As I understand it, the reason an HIV vaccine has been so difficult to create is that HIV mutates so easily. I understand the basics behind how mRNA vaccines are generated, but I don't understand why this approach would be expected to have any more success in evading the high mutation potential of HIV than other vaccine types. After all, it was even a concern with new coronavirus variants that the original Moderna vaccine would be less effective against them (and, indeed, while the original vaccine is still highly effective against all variants, my understanding is that it is less so than the original variant). And SARS-COV-2 mutates much less easily than HIV.
Can someone with more knowledge explain the thought process behind this?
There's some known HIV "bnAbs", or broadly neutralizing antibodies. The thing is, these are not the antibodies most humans develop in response to HIV.
Previous HIV vaccine attempts have only done a fair job at eliciting these broadly neutralizing responses. e.g. SAV001, a "whole killed" HIV vaccine, only produces broadly neutralizing antibodies in about a third of recipients (and less broadly neutralizing response in a much bigger fraction).
The mRNA approach, like some recombinant approaches, seeks to generate just portions of envelope protein to tailor the response to produce these bnAbs.
>An "elite controller" is a person living with HIV who is able to maintain undetectable viral loads for at least 12 months despite not having started antiretroviral therapy (ART) . Elite controllers are rare: for every two hundred people living with HIV, approximately one may be an elite controller (0.5%).
> It is not entirely understood why some patients are able to achieve undetectable viral loads without ART.
As long as they take their daily ART pills, they are safe from AIDS in specific, which is basically a death sentence. But things are not black and white. Someone who has ever been HIV positive counts as immuno compromised for their entire life. Studies have shown that there is basically no shortening of life expectancy, if you start ART early enough in the process.
> if the person with HIV started ART with a CD4 count above 500, they would be expected to live to the age of 87 – a little longer than those without HIV.
This might maybe be because a lot of effort is now poured on mid to end of life care, with the improving life expectancy? So the science behind pushing along a decaying body gets better?
My lovely wife is a live-liver-transplant kid and I too hope she outlives us all. Alas the 'organ preserving' drugs (the ones you take to help kidneys handle immunosuppressants) have difficult side effects. I'm not talking incomfort or pain, but pregnancy-terminating. Not the best way to end your first pregnancy...
And as it's 'just' prevention, it's hard to know whether it will reliably improve this individual outcome...
Viral load. Number of viral copies per volume of fluid.
Merely exposing someone to a virus does not necessarily result in widespread infection. A low enough number of copies could be neutralized by the host's immune response before it has a chance to spread significantly. How low this number is depends on the virus. For example, COVID-19 load is higher in symptomatic patients.
Chronic viral infections are managed by reducing as much as possible the number of viral copies in circulation. Risk of transmission is mitigated when number of copies is low enough. There are studies showing risk of HIV transmission approaches zero when HIV load < 200 copies/ml. Ideal would be HIV load < 50 copies/ml or undetectable.
At that low virion count it’s more about the probability that a virion will attach to the correct CD4 receptor and be able to work inside the cell. It’s not about the host's immune system defeating or being defeated on a number basis.
There is an "independent action hypothesis" in virology. It states that each virus particle (virion) has an independent probability of starting the infection in the body.
So it it turns out true, there is no "safe level" - we could talk about an extremely small probability, but it would still be higher than 0 - not exactly a risk one would like to take.
Yes. Assume 1 virion has a 0.001 chance to start an infection. You could infect 1 person with 692 virions, resulting in a 50% change of them getting ill (1-0.999^692). Or you could infect 692 people each with 1 virion, with 50% chance of at least 1 of them getting ill (35% chance: 1 ill, 12% chance: 2 ill, 3% chance: 3 ill, ...).
CDC backing up this claim. Having an undetectable viral load prevents transmission during sex —- but likely not during needle sharing. The answer to why seems to be an obvious “because there are less virus particles”. I’m linking a couple of scientific studies following couples having condomless sex where one partner is HIV positive, on ART with low viral load. Among the about 2000 couples in these studies there were no transmissions.
It does sound suspiciously like wishful thinking though, doesn’t it? You can’t sample all parts and all fluids of someone’s body all the time. Maybe trace undetectable levels of the virus can be transmitted, and of course they are going to look like a “no transmission” case if you lack the ability to detect that amount of virus. And that’s either not a problem (if trace levels = no symptoms), or a ticking time bomb waiting to find a host with the conditions that would enable mass viral replication back up to detectable levels.
There is no such thing as a trace/undetectable transmission. These studies have been going on a long time now with large numbers of participants, replicated in multiple countries/different populations. The results are very strong and not based on measuring viral levels.
The standard you are applying is literally not possible to imply anywhere.
Hell, an HIV viron could be created spontaneously through quantum tunneling in your body with some non-zero probability. I think it would be legitimate to triple equal signs that to "not going to happen" though.
Be careful. The infinite sum of epsilons over an infinite domain and over the time domain can and usually does converge to a finite value in real life.
Also, you can avoid having sex with a HIV-positive person. You can probably not avoid driving. So the fact that a risk may be low is not sufficient to take such risk if you can hedge against it.
It is because everyone dies relatively quickly that you can ignore ultra low risks. Suppose your lifespan was potentially 1 trillion years, how low would your risk tolerance need to be?
Meanwhile doing some once a day with a 1 in 1,000,000,000 chance of possibility killing you in 40 years just isn’t worth considering.
> Suppose your lifespan was potentially 1 trillion years, how low would your risk tolerance need to be?
Depends what your quality lifespan is. If I get sick of everything, that time isn't worth much.
There's also a "time-value" of life.
Cool stuff I can do today may be worth a lot more to me than things I can do 500B years from now. Especially since the person that would be doing them is someone I cannot identify with at all.
I don’t think most peoples 25 year old self can really identify what their 85 year old self will be like. Yet saving for retirement isn’t just about them some time in the future it’s about making you feel better now.
> I don’t think most peoples 25 year old self can really identify what their 85 year old self will be like.
Yes, and I believe this is a reason why people make choices that adversely affect their 50 year old self. Who's that guy in the future going to be? Why should I care about making it better for him?
You could say the same thing about people drinking heavily only to wake up the next day with a massive hangover. So it isn’t the differences between them that’s causing people to screw over their future self.
I can't comprehend 1000-year-from-now me. I don't think I would take many actions to improve life for 1000-year-from-now me even if I knew I could live millennia. Doing so does not buy me any comfort today and does not let me "give" to any person that I identify with or recognize as part of me.
I can imagine time scales on a par with how long I've lived and to a lesser extent to the ages of people I identify with.
(500 year from now me would see the first paragraph as exceptionally foolish... and also inevitable. But that fact doesn't change the truth of what I'm saying).
We feel fairly comfortable in stating that HIV is not transmissible surface-to-surface despite the mathematical fact that strictly there is some miniscule non-zero chance that it could be, this is basically the same thing.
You need to transmit a certain amount of HIV particles to cause infection. It is called inoculum. In normal sex, it is quite a lot, I wasn't able to find an exact number, but it is in tens of thousands in ther least.
The vast majority of virions seems to be killed by the immune system before they can actually take hold.
Thing is I wonder if a higher vitamin A and zinc intake can help because all epithelial cells need retinol (vitamin A), zinc is needed to move retinol around the body as Retinol Binding Protein (RBP) for epithelial cells. Alcohol can reduce fat soluble vitamins stored in the liver which can then reduce the VitA stored in the liver, you see this most easily with alcoholics and hypovitaminosis A, but even short term binge drinking can reduce levels enough to increase risks of transmission which probably explains man flu!
I found a cadaver study where they measured vitA content in the livers of dead people but didnt say how they died, knowing that you can die from ingesting too much vitA in one go like some arctic explorers did when eating polar bear livers decades ago and died. In order to get the highest amounts of vitA seen in some of these cadavers, you'd have to consume 30,000ui of VitA every day for at least a year without your body using any! Thats a lot of Vit A!!!
Anyone who paid attention to the Ebola outbreak in Africa a few years back, may remember that some viruses like Ebola can hide in parts of the body where the immune system can not go, namely the eyes and the testes and sometimes the brain, so they may have remembered that blokes testing negative for Ebola but previously had it, could still be passing it on through semen.
The thing with HIV, its typically passed through anal intercourse, not vaginal where there is sufficient lubrication, but its passed more frequently in Africa because they have a tendancy to have dry vaginal intercourse, because they actually try to reduce the wetness of the vagina which then creates microtears and sores and then its easy for HIV to get into the bloodstream, just like cuts and sores in the mouth also making it easy for HIV to get into the blood.
The whole 80's govt advice/warnings on HIV were directed at everyone because they didnt want to stigmatise those engaging in non vaginal intercourse.
The biggest risk from HIV is getting it into the blood, like most things which are pathogenic.
Now you can still have a highly effective immune system which can lock down viruses, but there is always the risk it gets into those parts of a body where the immune system cant go and I dont know what they test now a days.
> The whole 80's govt advice/warnings on HIV were directed at everyone because they didnt want to stigmatise those engaging in non vaginal intercourse.
Gay people were so stigmatized at the time that the government did nothing when they thought it was a 'gay disease'; they just let an epidemic spread and people die. Very few in the 1980s worried about offending gay people. Once it was spreading to people who weren't gay, then I'm sure health information was provided to those people.
Its like genital mutilation. These are legacy solutions when legacy forms of govt/social control like religions, royalty or cults were the main educational source for surviving back then. Ironically there still is some truth in things like religious fasting provided your glutathione levels are high enough.
There's no excuse for it in todays day and age, but what can you do? I sometimes think democracy is a soap opera for serious people, whilst the military run the real show.
Some cultures believe lubrication is a sign of poor virtue or infidelity. Women use chalk, cornstarch, etc, to ensure they stay dry and to (supposedly) enhance the pleasure of their partner.
There was a thing not long ago where talcum powder, I think Johnson & Johnson, had some asbestos contamination (asbestos being another mineral that can come from the same mines, apparently). And people were suing because it gave them cancer of the uterus and other internal parts of the female reproductive system. Which makes you go: Wait a second. How the hell does that happen?
I find it hard to believe. Wouldn't it make more sense that the powder was in contact with the external reproductive parts for extended amounts of time (which is its normal usage) and as a result some parts managed to get inside?
I don't think people are intentionally pushing talc through their cervix, if that's what you mean. But, pack your vagina with the stuff every day, and I imagine you can have all kinds of problems. If I were to go any further than that about exactly how it works I'd be speculating.
OK, I see. Because back in the day it was more or less standard to use powder in the groin area and leave it for hours in order to prevent skin irritation in babies, especially in the summer. So since it was standard usage, people should reasonably expect that the powder sold for this purpose was sufficiently examined and fit for the purpose.
When I first heard about asbestos in children talc powder, I simply thought it was just one of these "bad pharma" conspiracy theories (there was another one - about asbestos in sanitary towels). It seemed so far-fetched - who in their right mind wouldn't make sure to thoroughly check a product designed to have long-term contact with babies' skin against well-known carcinogenic substance? Well, it turns out this time it happened not in China but right in the heart of the USA.
> Anyone who paid attention to the Ebola outbreak in Africa a few years back, may remember that some viruses like Ebola can hide in parts of the body where the immune system can not go, namely the eyes and the testes and sometimes the brain, so they may have remembered that blokes testing negative for Ebola but previously had it, could still be passing it on through semen.
Nothing would surprise me! I know a mad scientist who works at the UK's Porton Down, we discussed alot, but the systems are not in place to stop people shipping stuff around. Until such times as that happens, any country with the know how can release anything anywhere.
I think this Hollywood film Dont Look Up will be a poignant message to everyone.
I mean, technically, there's always a possibility of getting HIV. Particles in your body could spontaneously quantum tunnel at the same time into the form of an HIV virus. This is basically impossible, but not actually (p = 0.00) impossible.
At some point you have to look at a probability and say - that's basically not transmissible.
That seems like a big if? maybe 0.5% of people actually are succeptable to the lowered viral load. Have studies been done that would detect such a population?
One reason we believe this is that we can typically detect virus quantities way too small to reliably replicate in culture, and believe that in vivo infection is even harder than in culture (because of innate immune response and the body not being composed just of the most susceptible cells).
You generally can't measure infectious dose directly without a highly unethical challenge study. You can sometimes know concentrations that did or didn't result in infection in various real world scenarios, and sometimes you have circumstantial evidence (e.g. you can know how much virus a person sheds, and what proportion of a room with certain ventilation quantities got infected).
The usual way of achieving undetectable viral load is via anti-retroviral drugs and I think this works in most people, at least so long as they get early enough treatment and keep getting it. The main reason to measure viral load in the first place is to get an idea of how well the drugs are working and if they need to be changed.
that's what I would think, it's got to be quantifiable: some sensitivity metric of the concentration of virus particles the device can detect vs the minimum quantity which is needed for infection. It's clear we can articulate these matters in the abstract, how does one go about actually measuring such a thing?
Undetectable sometimes means less than 200 or less than 50 viral copies per ml (depending on device sensitivity). In contrast the peak in the acute phase is 10^7 copies per ml (and settles to around 10^5 in the chronic phase), the probability of transmission is infinitesimal. There are many studies following very high risk cohorts (sex workers, intravenous drug users, etc) that have been able to empirically confirm this.
Detection means there is enough virus physically present in the sample for the detection technology to identify it.
Infection requires virus particles to be physically present in transmission vectors (fluids, droplets, etc). There's generally also a dose-response effect where more particles means more chance of evading the immune system well enough to establish replication in the victim.
So a lack of anything to detect, means a lack of anything to spread an infection.
> So a lack of anything to detect, means a lack of anything to spread an infection.
One should add that for that the threshold for detection has to be lower than the threshold for infection.
Example: let the detection threshold be 10 particles/ml and the infection threshold be 100 particles/ml (*) -> then undetectable implies that it is very improbable that an infection will take place.
(*) This is a very crude description. Think of it like this: Every single virion (virus particle) has a very low probability of causing an infection itself but there is a high number of them and for one them it might just work out (higher viral load -> higher risk of successful infection)
I'm not a biologist and this is based on general knowledge and some quick google searches but:
We're quite good at detecting viruses if we really want to. PCR can amplify DNA so much that we can detect even 50 viruses per milliliter of blood. A milliliter seems like actually a lot of blood to get into someone else and your innate immune system is capable of finding and neutralizing small amounts of contagions relatively well even if it's never seen it before. I do suspect this is a statistical impossibility though probably you could somehow get incredibly unlucky, for example in your blood momentarily all the free floating viruses end up in the same bit of blood and that somehow gets into someone else, but I think we can all realize that probability is tiny and in practice I don't think there are any examples of transmission with undetectable levels of HIV.
Well put. We can actually detect well below 50 copies/mL in the laboratory setting as well; we don’t go below this to maintain adequate test specificity and sensitivity in the clinical setting.
Not to put you on the spot but from my cellular bio lab I took it felt like PCR should be capable of detecting literally a single example of the targeted bit of DNA in the sample. Is the problem with detecting below 50 that the sample is too easily contaminated or is it that the primers can spontaneously bind to things they aren't supposed to at a high enough rate to invalidate the results?
There is no data that supports this assertion whatsoever. There is a lot of evidence going against it. Theoretically it may be possible, but the probability of this is on the order of 0 and so close to 0 it will likely never happen.
Think of it like chemistry. Sure, two covalently bonded hydrogen atoms at STP could have nuclei 1cm from each other due to random chance. However, the probability of this happening is so low that it is effectively 0.
If one bounds the risk from HIV from an undetectable partner to an unmeasurably small epsilon, dwarfed by other risks by many orders of magnitude--- the edges where the assertion are false don't matter.
I'm going from memory, and I can't remember how many years ago I saw this on television, but I thought it had something to do with a genetic mutation that likely gained a foothold in the Western European population sometime around the plague of the Middle Ages. If I remember correctly, if a person carried one copy of the gene, they could get infected with HIV, but it wouldn't develop into AIDS. If a person carried two copies, they would not even get infected with HIV.
> "these are not the antibodies most humans develop in response to HIV."
In many cases. One case, for example was identified from a prostitute in sub-saharan africa who managed to be completely HIV-free. It turned out she had a mutation in her antibodies that caused the antibodies to latch onto things with four sites instead of just 2 (think X shaped instead of V shaped).
That's why I said "most humans". bnAbs are generally antibodies that are detected in (few) humans. In addition to the people with seeming immunity through missing receptors or unusual antibody morphology, there's also about 1 in 200 infected that are "elite controllers" that do not develop high viral loads or severe symptoms when infected by HIV-- generally in large part to their bodies making multiple bnAbs.
Specifically it's advantageous because bnAB development requires 2 separate immune stimulii applied over months. Injecting protein bolus (traditional vaccines) then requires something like 6+ separate, different vaccines - so 6 synthetic paths, production lines etc.
mRNA eliminates all of that. The 2 immune pathways can be combined into 1 vaccine, and the multiple vaccines can all be produced with the same synthetic pipeline and the same distribution and administration requirements.
Yep. In fact mRNA vaccines are almost trivially easy to produce. I know for a fact that many biology labs around the world bought the reagents needed to make homebrew mRNA vaccines in earl 2020. Just in case big pharma screwed up. It would have only been a few days work for them to produce it for themselves and I wouldn’t be surprised if some American and European labs actually did it.
mRNA vaccines don't use regular mRNA though, they use nucleoside analogues to avoid triggering an innate immune response to the mRNA itself. is it really that easy to homebrew that? plus encapsulating it into lipid nanoparticles etc. sounds like it'd be a major project..
The lipid vesicles part is pretty simple I think. You don’t need it to last a long time, just long enough to snort it up your nose.
I am not sure about the XNAs. You might be able to get around it with increasing the dose (trivial if you are producing your own RNA) or it might be possible to use XNAs in a standard synthesis protocol. It would depend on the RNA Pol I think.
> Can’t you grow the peptide of interest and package it in a traditional vaccine?
Traditional way to do this is recombinant approaches (mentioned). These are also in progress. mRNA is much quicker to iterate, though. They tried a few candidate sequences in sHIV to guide their human vaccine development.
mRNA vaccines are kind of neat in the way that they create a few day long pulse of new virus-like particles showing up, to ensure the immune system gets really annoyed.
Strictly speaking you can, and not knowing the exact reasons this approach is moved to human trials where others have not, I can only conjecture.
However, the mRNA vaccine may be more stable in a way that makes it easier to make or store or for entrance into the body. Not to mention purification steps may be easier. You don't need to make this in some exotic cell line which creates a protein soup you have to purify. It may be easier on the body (less likely to develop a severe immune reaction), or it may be better at generating a sufficient immune reaction because a lot of mRNA development has gone into finding molecules that are readily taken up by the immune system regardless of cargo.
These are a few reasons I can think I am sure I am missing some and there may be a stated answer out there that I have yet to search for.
> this approach is moved to human trials where others have not, I can only conjecture.
Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches). They early ones showed no efficacy; the newer ones we just don't know (yet).
The main benefit of mRNA is iteration: you can try a whole lot of different protein mixes and see what works best in an animal model. A secondary benefit is that the sustained churning out of proteins for a few days seems to generate a much broader antibody response, making getting some of those elusive bnAbs more likely.
A big problem with killed HIV vaccines and purified fragments of HIV is that growing virus in human immune cells is extraordinarily costly, and you really wouldn't want to have some live HIV leak through your purification process. So this is why we're mostly talking about other approaches to make proteins (viral vectors, recombinant DNA in bacteria and other cells, mRNA vaccines, etc)
>Actually, a whole lot of recombinant approaches have moved to human trials (along with viral vector approaches).
I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA. But thanks for the clarification. And the mention of viral vectors which are an area I was less aware of till recently but it has been cool to see them in more places.
> I should have been more clear here, I meant specifically trials of what I presume could have been attempted if the vaccine was expressed as protein instead of mRNA.
Yes, and one vaccine approach is getting a bacterium or other virus to make a lot of a protein you're interested in, and then purifying the stuff you're interested in and forming it into a vaccine product. These are recombinant approaches. E.g. https://en.wikipedia.org/wiki/AIDSVAX is exactly what you describe: a viral protein vaccine developed using recombinant approaches from e.g. Chinese hamster ovary cells https://pubmed.ncbi.nlm.nih.gov/8142140/
The first was a hepatitis B vaccine developed in the 1970s where yeast cells were modified to make hepatitis B proteins. Then the HPV vaccine used the same approach, choosing proteins that would spontaneously assemble into a virus-like particle that triggers a strong immune response.
Complicated proteins have to come from a living thing, in practice. So if you're going to administer a viral protein, it has to come from purifying virus that you've grown or from a recombinant approach of some kind (and growing HIV is problematic for multiple reasons).
Viral vector vaccines are going to stimulate the innate and intrinsic immune system and you're going to get things like IL-6 release and apoptosis of the "infected" cells without generating any humoral repsonse to produce T-cells, B-cell and neutralizing antibodies.
mRNA vaccines are particularly useful because you can substitute bases with N1-methylpseudouridine which makes them identify as "self" by TLRs and doesn't generate counter-productive innate immune responses. You do need an adjuvant so that the cell produces more MHC displaying the antigen and attracts lymphocytes but the nanoparticle works to do that.
The result is a very small message payload to the immune system that targets the correct system. Viral vectors all have more "stuff" all over them which are going to trip other parts of the immune system (or cause side effects like the PF6 interaction with the Adenovirus capsid that is responsible for the rare clotting effects).
I’m not a doctor, but as a gay man: it’s my understanding HIV doesn’t mutate in the same way a disease like Covid does, at least not in the sense that there’s as many opportunities to spread (i.e. not airborne), so while HIV may actually mutate more in theory, it gets less chances to spread, so less completely-different variants become widespread.
Also, as part of “stopping the spread” PrEP has existed for years. It’s still proven to be effective protection against contracting HIV even if directly exposed (though it’s a pill that must be taken every day rather than a vaccine). There’s also PEP that helps make you undetectable (untransmissable) if you do contract it (and as such, it’s no longer what many people still mistakenly regard as a death sentence).
I honestly don’t know why everyone who is sexually active isn’t on PrEP (the federal government even mandates it be free to those without insurance in most cases)— it should be as common practice as wearing a condom and birth control, yet its existence isn’t even known to many people (especially among straight people).
>I honestly don’t know why everyone who is sexually active isn’t on PrEP
Side effects. People generally don't like to take drugs to prevent things if the chances of acquiring the illness is minimal. For example, if we had an approved vaccine for Malaria, we wouldn't just give it to everybody in the USA, and even if we did, many would not take it.
I had a physician explain that you need to treat the whole person (ie. address symptoms, serious issues, anything demonstrably problematic) because otherwise almost every person could be diagnosed with something and prescribed medications for. If you look for physiological abnormalities, you’ll find some. It’s why he said doctors discourage loading up on useless tests for no reason.
And then you risk creating more side effects in an otherwise healthy, complaint-free person.
A for-profit healthcare system wants this. Which is probably why the States medicates and prescribes so much more compared to other regions.
Small correction: PrEP (pre-exposure prophylaxis) and PEP (post-exposure prophylaxis) are both protocols for using drugs to prevent infection. You generally take PrEP drugs every day if you think you're in danger of being exposed, or alternatively take PEP if you think you have been exposed to HIV without any kind of protection, sort of like a morning after pill (but every day for a whole month).
It's a post-exposure treatment, don't think that qualifies as a cure. Same thing with the rabies vaccine, it'll only save your life if given before any symptoms occur (and the disease has entrenched itself in the body).
I agree in that no straight people (that i know) consider PrEP, although according to a quick search the HIV prevalence rate is twenty times lower in my country compared to the US.
Obviously the human brain statistician goes out the window when comparing a lifelong illness with a few hours of discomfort, but would it be generally safe/worth it to put the entire population on PrEP during sexual activity? I heard that HIV patients have noticable side effects with their meds.
As a person on PrEP, it is only recommended for people at higher risk of HIV. In the West, that does not include sexually active straight people unless you have other confounding factors (e.g. IV drug use, partners who are at higher risk, etc.). Essentially all gay men (or, more accurately, "men who have sex with men") are at higher risk, which is why it is recommended for them.
Gay men living in cities also have many more sexual partners than the rest of the populous.
The men I’ve met who have had 1000+ partners is exclusive to gay men. I’ve yet to meet a straight man who isn’t a celebrity that has gotten anywhere near that. Yet this order of magnitude (100-1000) is common among gay men.
The risk levels for your average young straight man in the west are obscenely low these days. You’ll have sex with maybe 10 people in your entire life if you’re a try hard. Chances are astronomically low for most straights - especially if you practice safe sex until both parties are tested and monogamous.
Straight people aren’t concerned because they’re simply not having that many sexual partners.
Less than 10% of all male HIV cases came from having sex with a woman. Yet men who have sex with women are 95%+ of the population. There’s a risk but it’s really low. And I think it’s even lower now with the ways things are going - straight male millennials and zoomers are having less sex than any generation before it that we know of.
A lot of this is grossly exaggerated and anecdotal, and actually rooted in homophobic tropes from the Reagan era so as to dismiss HIV as a “human disease” and instead condemn it as a “gay disease” that the LGBTQ+ had coming its way. The average US gay man has had no significant number of sexual partners more than the US straight man, and this has been backed up by study after study. Do you have actual sources?
Anyways, in absolute numbers now there’s more heterosexual people who are testing positive for HIV than gay people in the West (and it’s been the case globally for a while, too)
I would also add East Asia (China, Japan, South Korea, Taiwan, Hongkong, Macao) to that list. The rate of HIV positive ("seropositive") status is still incredibly low. Ignore China for a moment because it is hard to believe any of their official gov't stats! These countries are definitely much more sexually active (more lifetime partners) than more socially conservative neighbors in South Asia (Indian subcontinent).
Interestingly, in these countries, there is still ready access to sex workers in any medium-sized city and above, yet infection rates are still very low.
I must confess: I wrote the above post strictly about heterosexuals. I have never read anything seropositive rates for gay men in these regions. (I write the last sentence with the assumption that gay women have a tiny risk to contract and spread HIV.)
Well, in absolute numbers, recently heterosexual people are more prevalently diagnosed with HIV. Likely because they don’t know about PrEP in the first place, and then decided whether or not it’s for you. https://www.independent.co.uk/life-style/health-and-families...
HIV/AIDS is extremely rarely (maybe never) sexually transmitted in female-female intercourse. The CDC notes a "negligible" risk of transmission from sex toys.
HIV/AIDS is contagious through vaginal intercourse. Transmission is fairly low, though certainly not risk free, because most people aren't bursting blood vessels during typical vaginal intercourse. It does happen, though.
HIV/AIDS is most contagious through anal intercourse, and especially for the receptive partner. This is, as far as I know, regardless of the sexual orientation of the participants (presuming there's an actual penis involved and not a toy).
Another thing to consider is it isn't a life long illness anymore. It's a life long subscription to a drug which neutralizes the threat and lets you live an entirely normal life without any problems other than having to take the drug periodically forever.
Certainly not ideal but its not like you suffer illness.
Most of these things the medication only helps some amount. For HIV it's meant to be 100% effective and makes it undetectable to testing. All active HIV is killed and only inactive HIV remains but inactive HIV doesn't harm you, it only seeds a new active infection.
And in most countries the treatment is funded by the government.
Because most straight people don't need it, risk is much lower. Truvada is nephrotoxic and that's bad in the long term, many drugs are bad if taken for long periods. Condoms have no such side effects.
Truvada can be a bit hard on the kidneys. Before starting it you generally have to have some blood work done to check to see if you're likely to have issues, and at least for a period after starting it they usually want to do blood tests regularly to ensure the kidneys are functioning properly. So it's certainly not something that everyone can get.
Descovy appears to be better, but I think it's not approved everywhere yet.
'should be as common practice as wearing a condom and birth control, yet its existence isn’t even known to many people (especially among straight people).' - not sure if you've seen who HIV effects, but if it especially effected straight people in the west (straight people in africa know full well about it) they would know about it.
"Prof. William Schief explains how the novel #HIV #vaccine being tested in human clinical trials can trigger the right #Bcells of the immune system to achieve the much sought after broadly neutralizing #antibodies."
One reason is that mRNA vaccines can be developed much faster than traditional vaccines. So the idea is you have a better chance of "outrunning" a strain.
I think slowly will come the realization that mRNA vaccines aren’t as fast to develop as people thought. Sputnik/AstraZeneca vaccines were released almost at the same time as Moderna/Pfizer. Yes, the latter were first commercial mRNA vaccines, but the technology is nevertheless rather mature. I watched a lecture by the people credited with creating mRNA vaccines and it turns out people have been working on the technology for decades.
Now, the thing is that you can’t just sequence a virus, do bioinformatics, synthesize mRNA and package it into a nano particle. I mean, you can, but chances are it’s going to fail like the CureVac vaccine. The mRNA that gets packaged needs to be modified (I believe with alternative bases) to achieve desired effect.
If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.
One single employee at Pfizer created 10 vaccine candidates in one day.
> Now, the thing is that you can’t just sequence a virus, do bioinformatics, synthesize mRNA and package it into a nano particle.
You can, and that's exactly what was done. However, out of the 10 or so candidates, they selected a few of the more promising ones to continue research.
They are fast to develop. However, there are other steps in the pipeline that aren't so fast.
> The mRNA that gets packaged needs to be modified (I believe with alternative bases) to achieve desired effect.
That's the easy part. The full mRNA sequence is not that large (https://berthub.eu/articles/posts/reverse-engineering-source...) and many of such substitutions can be done by algorithms. Now, maybe the modified protein won't fold right. That's not as easy (although, we can compute how it will fold now).
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants.
If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics.
I think you underestimate the effort needed to create an immunogenic vaccine candidate that doesn’t have unwanted side effects. That’s one of the reasons CureVac failed: https://www.nature.com/articles/d41586-021-01661-0
And yes, AlphaFold is a major milestone, but I don’t think we’ve solved protein folding for good.
> If we were reckless and just wanted to inject someone with the latest update, this could be done in a matter of days. Human trials took months and people still complained that it was 'developed too quickly'. Then there's logistics.
I'm sure there is also the commercial concerns about cannibalising their own product. Would you take the 1-strain BioNTech vaccine if you knew that a 5-strain is also in circulation?
The article you linked is a reckless oversimplifaction of the mRNA vaccine development process. In my opinion, it is dangerous towards an understanding of mRNA vaccines and how they will impact our future.
First, BioNTech (not Pfizer) had 10-15 years to research, develop and test vaccines against new zoogenic Corona viruses. There was literature regarding the modification of the spike protein even before SARS-CoV-2 hit. BioNTech had either SARS or MERS candidates years before the pandemic.
Second, we cannot compute "how it will fold" either.
Third, discussions on HN always, always leave out the hard and messy parts: Wet lab and patient studies.
I am a huge fan of mRNA vaccinations, but the understanding of their potential is hugely different between the "hacker world" (HN, Twitter computer scientist bubble, etc.) and the biology world.
Both the Oxford-AstraZeneca vaccine and Sputnik are using a pretty similar trick that gives them the speed-up. They still get to pick an arbitrary sequence, but they're smuggling it inside a virus instead of as mRNA.
That's why the codename for the AstraZeneca vaccine is ChAdOx1, it's a Chimp Adenovirus as host for the sequence. Take this mild uninteresting chimpanzee virus, but tweak it to tell human cells to produce your arbitrary sequence instead of itself. The humans become immune to whatever your sequence was (and maybe to Chimp Adenoviruses?).
I'm sure there are reasons this might be better in some cases, and it involved less bleeding edge technology which made it a safer bet in a pandemic, but the mRNA approach seems obviously more general and even perhaps more re-usable.
Which is a major problem with this technique. One of the other vaccines (J&J?) used a relatively harmless human virus and as I recall, some people with previous exposure had no effect from the vaccine.
Likewise, it would seem that after one vaccine using a given vector, completely unrelated vaccines using the same vector would be ineffective? So presumably they would eventually run out of all the accessible vectors.
"chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 5 (HAd-V-C5) and human adenovirus type 26 (HAdV-D26) — the scientists found that ChAdOx1 had a strong negative charge, which meant that it attracted PF4, which has a positive charge."
> but the mRNA approach seems obviously more general and even perhaps more re-usable
We should also see how subunit protein vaccines such as Novavax will perform once they are widely available. From what it looks they should be equally effective and more anti-vaxxer friendly.
> Sputnik/AstraZeneca vaccines were released almost at the same time as Moderna/Pfizer
Most of the time and cost is associated with the trials - not the actual development AFAIK.
What would be more promising is if MRNA proves to be much more likely to pass trials. I think we need a lot more attempts at different viruses to have an idea here.
Certainly - if this HIV vaccine /does/ work - that's a huge win for MRNA.
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.
This is nonsense. The traditional vaccines don't work any better. They're worse. This is evidence MRNA is better than traditional vaccines.
Didn’t say they were. Rather that mRNA don’t seem to be approved faster for the new variants.
> This is evidence MRNA is better than traditional vaccines.
Haven’t been following the field that closely. I only seen one pre-print(probably Hungary?) where Sputnik was on par. Would love to see data if you’re willing to share.
Edit: I admit I’m a bit confused since I mixed “traditional vaccines” and Sputnik/AZ together. The latter aren’t traditional since adenovirus-based vaccines haven’t been previously deployed, same as mRNA vaccines.
> Rather, there would be delta- and omicron-specific vaccine.
I think there are -- they just haven't made it through the trials and approval processes yet. These are press releases from Pfizer for whatever it's worth:
Regulation will take time to catch up. We manage to create and approve a flu vaccine every year, and that's likely because the general process has been approved, and so each iteration is fast tracked. I don't think that's the case with mRNA vaccines yet.
you can't do this since you need studies and those take time. Depending in the size of your cohort and the current viral load in the population. Curevacs study had the problem that during this time in germany the corona-virus wasn't that common so nobody knew whether the vaccine is working.
As I understood it, the actual vaccine was developed super quickly and then everybody waited for the results of the study.
I assume that still has something to do with mRNA being a novel vaccine type. Therefore the regulatory bodies are still carefull. If Moderna, Biontech and other potential players show again and again that there process of developing new vaccines is safe, I'd guess the time to market will getting shorter and shorter.
The omicron and delta vaccines have existed for awhile now. The FDA requires efficacy testing for each individual booster. If the omicron specific booster isn’t better “enough” than a booster of the already approved vaccine, it’s going to be suck in approval hell.
Regulatory bodies need to adjust to the new speed of mRNA vaccine production if we want that sort of release schedule.
The way I understand is that that design and manufacturing is the smaller share of the lead time for mRNA and non-mRNA. The pre-clinic and clinic trials along with any regulatory delay take most of the time. Still mRNA vaccines are better and cheaper than conventional vaccines after CAPEX is done. Both Moderna and Pfizer have trials running for Omicron.
The slow part is the safety testing right? If we had a robust enough theory of vaccines safety we could reduce that. How are the yearly flu shots tested anyway? Now, I would not take such a HIV shot. But for high risk groups, think promiscious homosexuals, it may eventually be worth it.
I'm not from a bio-science area but AFAIK mRNA vaccines are robust.
1. The same mechanism of deliver is used so it's already tested and know to be safe/effective.
2. It replicates the same protein(s) found on the virus. So it will not due more damage than getting the virus and it will have a high probability of being effective.
Efficacy trials are quick for a disease with 100k infections a day. It's much slower for something that has that many cases a year. It's much harder to tell a statistical difference from noise when you're talking minuscule cases in trial groups.
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.
Is this a problem with mRNA, a problem with the approval-for-vaccine-variants process, a problem with funding, or a problem with the politicians who thought COVID would magically go away by August 2021 (Never mind that most of the world was nowhere close to being vaccinated, and the millions of sick people throughout it were happily producing variants)?
I am ignorant on most of these subjects, but I would be surprised if the mRNA part of that was the problem!
The annual flu shot indicates there is presumably a "same vaccine, slightly different strain" streamlined procedure that can be used. I'd expect the same to occur with COVID boosters over time.
> it turns out people have been working on the (mRNA vaccines) technology for decades.
if you mean "Developing mRNA vaccines from nothing to a working product" then yes, that's taken decades.
I don't really think that fact has much to say about if when you're already making millions of doses of commercial mRNA vaccines around the world this year, how fast next year's version can be made, tested, approved, manufactured at scale and deployed. The challenges involved seem to non-overlapping.
"delta- and omicron-specific vaccines" are coming soon, but this is still the very early days on mRNA vaccines, as a commercial mass-scale product.
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.
There are about 5 different false assertions in here with nothing to back them up.
The Israelis have found that a 4th shot isn't particularly useful in immocompetent healthy younger adults under 65. We're unlikely to have a 4th shot. This makes sense because in between the first dose(s) and the booster shot the immune system had time for the response to mature via hypermutation/maturation.
There's nothing wrong with the mRNA vaccines either since they're better for this virus than any other vaccine for this virus. The old school inactivate virus vaccines are worse than mRNA vaccines (although cheaper and easier to mass produce).
People compare mRNA vaccines to the polio vaccine but that is apples and oranges, since coronavirus is a virus that doesn't typically have a viremic phase (outside of severe multi-organ COVID). An appropriate comparison would be between coronavirus vaccines and flu vaccines. Comparing a coronavirus vaccine to a polio vaccine is just ignorant.
The mRNA vaccines are also wildly successful by the measure which matters most, which is protection against severe disease and death. They were never promised as being perfect against contracting the disease and transmission. You can lookup very public headline statements from Fauci in late 2020 before the vaccine trials were done setting expectations around a 50% vaccine efficacy against contracting disease.
We're also unlikely to be chasing after reformulating the vaccine for specific variants since by the time it could be updated and a hundred million doses were produced and shipped and we tried to get them into people's arms the variant wave would be over in that region. Just producing and moving the doses is a logistics problem that will take months. And the boosted response to the ancestral virus is still very strong against Omicron, and there's no evidence of any waning of efficacy against severe disease or hospitalization and no evidence of escape from T-cells (and the pattern of mutations in Omicron is random with respect to T-cell epitopes and shows no clustering).
The newspapers never should have sold vaccines as a way to stop the virus in its tracks. That isn't a problem with the science or the technology though. That is just that human emotions got out of control wishing for a magic shot that would make it all stop.
People often complain about the trials being cut short, but in fact we had enough data to determine the efficacy and safety outcomes. What we cut short was durability. Turns out the neutralizing antibodies and efficacy against infection/disease wane over 6-12 months (as it does with natural infection as well). That's the reason why the original 90% VE against infection numbers turned out to be wrong, we cut the studies short to start getting it into arms. The 90% VE against hospitalization/death have been maintained though.
Might have included a certain cardiologist on Twitter, but the notion is out there somehow and it didn't come from the scientists who know what they were talking about.
These days, notions come from many places besides journalists. Plus, lumping all journalists together, from the NY Times to the fly-by-night Russian propaganda outfits, makes the term 'news media' meaningless.
It seems you’re debunking the claims I’ve never made. My point was that it doesn’t matter that mRNA vaccine can be developed extremely fast compared to others, like adenovirus-based. The logistics and production will even it out.
Yes. It takes a long time to generate the flu vaccine. The strains need to be selected long before the season starts so it's a bit of guess work. That's why effectiveness varies from year to year. mRNA vaccines can be produced in high volumes much faster than traditional vaccines. It would allow the flu vaccine strains to be selected at a better time.
Why the /s? I don't think there is a sure way to estimate what the number of total symptomatic infections would be if there weren't any vaccines, but the fact that unvaccinated are overrepresented in case statistics indicate that the vaccines are working as expected.
> One reason is that mRNA vaccines can be developed much faster than traditional vaccines. So the idea is you have a better chance of "outrunning" a strain.
Is that why the response to Delta was "just take another dose of the original formulation" and the response to Omicron was "just take another dose of the original formulation until we have the new one made up in a few months"? And who doesn't see another strain taking over in the next few months, rendering this new formulation less effective than originally promised?
My math may be off but there's been exactly one new Covid vaccine formulation in a little over a year, which is about how fast we crank out new flu vaccine formulations. Why exactly did we need to use mRNA tech to crank out new vaccines at the same speed as we did with traditional vaccines?
I suspect the fact that we're in the middle of a pandemic has something to do with this, though.
In particular, the demand is such that we urgently need hundreds of millions (or billions?) of doses. That takes a lot of effort to roll out. Most vaccines probably don't see use at that scale and speed. An HIV vaccine, for example, would probably initially only go out to communities with higher risk.
They have trialled variant specific vaccines for both Delta and Omicron. It turned out that the original vaccine is as effective for Delta, so that work was shelved. Omicron, on the other hand, seems to be evading the immunity created by the Alpha vaccine, so they are actually planning to start producing an Omicron specific booster (or more correctly Alpha+Omicron) after FDA approval.
> They have trialled variant specific vaccines for both Delta and Omicron. It turned out that the original vaccine is as effective for Delta, so that work was shelved.
No, it wasn't; in fact, the Pfizer-BioNtech Omicron variant-specifc vaccine and booster trial was announced only a week ago, while Novavax plans to begin testing an Omicron-specific vaccine imminently.
You said, well, exactly what I quoted, which was that variant-specific vaccines for Delta and Omicron were tried, found less effective than the the existing vaccines, and abandoned. That is false.
> I mentioned the upcoming Omicron vaccine too.
No, you said that after abandoning Delta/Omicron variant-specific vaccines, “they” decided to work on mixed Omicron/Alpha boosters. That is also false. Novavax is planning to trial Omicron-specific vaccine. Pfizer is trialing Omicron specific vaccines, both as sole vaccines and as boosters after existing vaccines. Moderna is, I think, working on an Omicron-specific booster-only (after existing vaccines) approach.
> which was that variant-specific vaccines for Delta and Omicron were tried, found less effective than the the existing vaccines, and abandoned
> It turned out that the original vaccine is as effective for Delta, so that work was shelved. Omicron, on the other hand, seems to be evading the immunity created by the Alpha vaccine, so they are actually planning to start producing an Omicron specific booster (or more correctly Alpha+Omicron) after FDA approval.
???????????
The thing he said may not have been strictly accurate but your claim about what he said is much less accurate than that.
> Why exactly did we need to use mRNA tech to crank out new vaccines at the same speed as we did with traditional vaccines?
mRNA tech is a lot newer than "traditional vaccines". I do not expect that the mRNA process is run at the same speed with the same degree of confidence at the same number of facilities. Yet.
- This isn't really the reason why mRNA is attractive here (see my other comment above). (Though, ability to iterate/try many protein combinations quickly in animal models was helpful).
- Almost no drugs or treatments do we really know the long term picture of. Running studies in a way that lets you detect effects far later in life isn't practical.
- When we're talking about treatments to prevent severe disease, bounding the consequences to be very, very likely to be well below the consequences of the virus times the likely infection chance is "good enough".
Not to mention the long term effects of COVID are known and way worst that what a vaccine can give you.
Vaccine are building an immune response, they're not drugs that try to cope the symptoms (eg. Panadol) and they are the safest drugs out there.
Is so interesting how people eat Panadol and many other drugs like candies (without reading the KNOWN side effects - which are also nasty), while they focus so much on things they know nothing about thinking that has mysterious "long term effects"
The one that really surprises me that people take like candy is Tylenol/Panadol/Paracetamol/Acetaminophen. It's the leading cause of acute liver failure in the US. Among common OTCs, its active dose is I believe the closest to its lethal dose. Just 2-3X the recommended daily upper limit can cause liver damage, and when taken around alcohol, the toxicity is dramatically higher.
I strongly doubt that Acetaminophen would be approved as an OTC drug if proposed today.
I never really gave much thought to how dangerous this stuff was until a year or so ago, Eric Engstrom (one of the creators of DirectX and a personal hero of mine) accidentally overdosed and died from it:
> He died at a hospital in Seattle. His wife, Cindy Engstrom, said he had injured one of his feet in October, accidentally took too much Tylenol for pain relief and suffered liver damage.
On the other hand, for some people Paracetamol (in the US Acetaminophen) works very well, and it's really cheap. So although there's been increasing oversight to reduce overdose deaths, I think you're going to keep seeing it available OTC in some form even though you're right it'd never get OK'd if invented today.
Once I realise that the Flu (or whatever) is inducing enough pain that I can't ignore it, or I start to run a serious fever, I take paracetamol to get on top of that, usually in the form of Lemsip because I'm bad at taking pills, Lemsip is cheap, and none of the other ingredients in ordinary Lemsip these days really do anything much, just the paracetamol.
I find maybe 1 or at most 2 of the "maximum" 1g (= 1000mg) doses a day gets the job done, which is well inside the indicated limits.
None of the OTC alternatives do it for me, they're not useless but the effect from the indicated dose is far reduced so I'm glad to have paracetamol. I've had fentanyl after surgery, which was certainly effective but seems like a very bad idea to have around the house, and Entonox after a road accident which again, effective but seems like a bad idea for OTC usage.
Fascinating, can you tell me more about your aversion to Advil? I haven never encountered anyone warning about it until now and would like to know more.
>"If you're concerned about vaccines but not about other common drugs, you're in need of some risk calibration."
The good news is that I am not concerned about the safety and efficacy of vaccinations. I misinterpreted your comment because of the way it was worded. This is because I know some over the counter pain medications, like Tylenol, can be dangerous. So, I assumed there was a risk to Advil that I wasn't aware of and wanted to know more, given your background as a Biochemist.
Yes and the known risks are calculated within the trials or after few days of usage. Definitely not 20 years after you've gotten the first pill. Would be pretty hard to correlate it to something that happened 20 years ago.
Other drugs don't have a better safety profile if they were tested for so long. If anything, it proves that is highly toxic for your body (similarly to many chemio treatments)
Knowing long-term effects (1+ years) is not a precondition of approval for most vaccines. It just so happens that vaccines usually take a long time for approval, so we end up knowing long-term effects as a side effect.
This is because there generally isn't a known mechanism for vaccines to have long term effects. Not ruling out the possibility, but we understand how vaccines work pretty well. Also, most vaccines are subject to a cost/benefit analysis anyway (we don't give the rabies vaccine out to everyone) so the miniscule chance of having long term effects has to be weighed against the much more likely long term effects of the disease.
> This is because there generally isn't a known mechanism for vaccines to have long term effects.
I know a lot of people believe this, but as a developer who regularly deploys code to production, this mindset blows me away.
I'm not saying that being a developer means I know anything about this. I'm well aware of my (our? I don't know what you do) peoples habit of thinking being good at our craft means we're also somehow suddenly good at others.
But if I told someone that I don't need to know the effects of v7.1.3 before patching it because I can't think of a mechanism for it going wrong, and besides, we already released all those other versions and they were fine, I'd hopefully be fired.
I get it, software and medicine are different things, and some things just aren't practical in meat space, but the mindset around testing is something that I think will always be difficult for me to understand after being in this occupation for so long.
> But if I told someone that I don't need to know the effects of v7.1.3 before patching it because I can't think of a mechanism for it going wrong, and besides, we already released all those other versions and they were fine, I'd hopefully be fired.
You are missing the point. If someone told you they are worried that your code is going to turn the CPU into strawberry jelly, you would be correct if you said 'there's no known mechanism that will cause that'.
Analogies are always flawed, but in this one, the pharmaceutical is the code and the human population is the set of machines its going to run on. The adverse effect would be an error that happens during runtime.
It's not quite strawberry jelly, but depending on the target you're writing for, you could destroy the actual hardware (think embedded devices).
If you presuppose that adverse effects can't happen, then sure, your quip makes sense. But pharmaceuticals having adverse effects isn't some unimaginable thing, it's expected and tested for.
>But pharmaceuticals having adverse effects isn't some unimaginable thing, it's expected and tested for.
Not for potential issues tens of years later, which is basically the concern people are raising about these vaccines. We instead look at known potential mechanisms that could cause harm and operate off of that.
We have studied the short term side effects of these vaccines, much we do anything else, and have looked at known potential mechanisms that could cause issues down the line, and have not identified any. This is more or less the same standard applied to just about any medical research for drugs, vaccines, other treatments, etc.
> Not for potential issues tens of years later, which is basically the concern people are raising about these vaccines.
I am concerned about tens of years later, but also about just ones of years later as well. We've done the best we can so far, and it seems like a clear win for some categories of people. For others, it's not so clear (like young healthy people with a previous infection living in the age of omicron for example. This is not medical advice, go to your doctor for that).
> This is more or less the same standard applied to just about any medical research for drugs, vaccines, other treatments, etc.
Sure, but I'm not chomping at the bit to take any more of those either (already had all the usual vaccines and then some, minus flu). And those other things have been around long enough that adverse effects eventually become unmissable. You see those occasionally in class action commercials.
I'm pretty sure understanding the biology behind it all can help make predictions about the outcome in the same way that you know that merging a pull request isn't going to bring the entire internet down. I mean, it could. But there's no known mechanism that will trigger such an event.
That reminds me of the first atomic bomb test. We weren't 100% sure that the atmosphere wasn't going to ignite with an atomic bomb, but those that knew the physics knew it was almost impossible.
> "If, after calculation, [Compton] said, it were proved that the chances were more than approximately three in one million that the earth would be vaporized by the atomic explosion, he would not proceed with the project. Calculation proved the figures slightly less -- and the project continued."
> I'm pretty sure understanding the biology behind it all can help make predictions about the outcome ...
Of course it can, that's what you use to write your test plan. But I never (ever) rely on those predictions alone. Everyone who has done this long enough knows that if you don't test your code well enough before you push it out, it will fail. Hell, it'll even fail sometimes when you did thoroughly test it.
Well, in computers our test plans generally run in seconds.
If you had to push code and wait a year for feedback then how you tested and pushed code would change dramatically.
Now imagine the environment you were pushing code to was
1. Always changing in very small ways that could sometimes have huge affects due to completely random variable changes you had no control over.
2. Every host your ran your software on 'could be' different in ways that are incompatible and you have no way of testing all of them.
Well said. But some people take this as "well we can't realistically do the exhaustive test, and we really want this thing, so let's assume the outcome will be positive". That's fine when it's your own choice, but it's not when you're forcing it on other people.
> But if I told someone that I don't need to know the effects of v7.1.3 before patching it because I can't think of a mechanism for it going wrong, and besides, we already released all those other versions and they were fine, I'd hopefully be fired.
But this isn't what they're saying. They're saying that there are few to no ways for it to not have any detectable issues for 6 months and then suddenly go wrong (which I'll note is also true for software!). Canarying and staged rollouts are a good idea in software, as they are in medicine. But much like you don't think its necessary to canary v7.1.3 for a year, just in case it has a bug that makes it shut down suddenly after 200 days, its probably not necessary to wait a year to see if a vaccine causes sudden acute liver failure after 7 months, because there just isn't a biological mechanism for it to do that (the vaccine is already out of your body by that point!).
And to the extend that such issues are possible (leap days can do weird stuff), we can look specifically for those mechanisms (like say monitoring for stuff that would lead to liver damage in the weeks after vaccination).
> But this isn't what they're saying. They're saying that there are few to no ways for it to not have any detectable issues for 6 months and then suddenly go wrong (which I'll note is also true for software!).
Over the years I've become a little obsessed with imagining the ways things can fail (I'm just as fun at parties as you can probably imagine).
An example that immediately jumps to mind where that is not true for software would be something that quietly uses some resource that you didn't expect (open ports, filehandles, space on disk/memory, the space inside of however many bits you have for a field, anything like that). These are things that you don't know to test until you've seen them fail, and only then can you start to automate.
One possible analogy here is cancer or autoimmune issues. If you get diagnosed with either of those today, they almost certainly started a while ago, they just weren't detectable until today. Or maybe they would have been if you knew exactly where to look, just like if you knew to keep an eye on how many ports you had left on your live server. (Not claiming these vaccines cause these things, I'm sure some peoples blood pressure started rising as they read this).
The complexity of software is nowhere near that of the human body or populations of humans, and yet it can be incredibly hard to predict. Multiple backwards compatible versions on the client and server side, running on different hardware with different operating systems, all of these things changing over time. Unexpected behaviors can absolutely show up at any time.
Of course you can't test it all, but you do what you can, and then after that you monitor very carefully, but its way more expensive to fix the problem after it reaches prod. In humans, there's a chance that its not just expensive, it's impossible.
Let's suppose that your software currently has an incident where the service is degraded. For every day you don't push a fix, you lose 0.X% of revenue.
Some engineer creates a fix by turning off some recently added experiment responsible for the service degradation. The rollback passes all unit tests and integration tests. You know this fix is low-risk (maybe because your service was healthy for the ~1 year prior to the rollout). Even if there is some risk that this rollback breaks the service at some point in the future, in comparison to the known revenue loss the expected loss of that breakage would be minimal.
Another engineer objects to the rollback saying that "they don't know of the long term effects of such a rollback." You try to counter their claims by showing that previous rollbacks were almost always successful, and when they caused another failure that failure was not nearly as bad as the original service degradation. Also, the rollback passes all tests. That engineer then repeats "we don't know of the long term effects of this particular rollback, and I'm skeptical that the fix is good because the failing experiment and rollback was identified so quickly."
(Rollback vs. fix-forward doesn't actually matter; the point is that all available knowledge shows that the fix is low risk, historically supported, and that there is likely no mechanism for random failure in 6+ months.)
Do you think it would be correct to prefer the second engineer's claims?
Yeah, I get your point, at the end of the day the net result is what we care about.
But the assumptions that you use to calculate that net are where all of the disagreements stem from. In your example, you've constrained it to losing well defined revenue, and "you know this fix is low risk", so the answer is easy.
Maybe (wrongly or rightly) you don't have faith in the revenue numbers, or in the test suite or the engineers writing the tests or the fix, maybe there's office politics involved, etc.
This thread started with my reaction to these lines from op:
> Knowing long-term effects (1+ years) is not a precondition of approval for most vaccines. It just so happens that vaccines usually take a long time for approval, so we end up knowing long-term effects as a side effect.
This is because there generally isn't a known mechanism for vaccines to have long term effects. Not ruling out the possibility, but we understand how vaccines work pretty well. [...]
I've seen this claim dozens of times, and it always always always makes me think of those scenarios where you find a bug in code that you or someone you trust/respect wrote from the ground up, and you wonder "how in the f*** did this ever work?". I'm not claiming I'm right to feel that way, maybe this is a defect in my character, but I just can't buy the "we understand vaccines pretty well" thing.
I think the place where the disagreement or misunderstanding lies is in how we're describing thinking about unknowns.
You seem to be taking this from the perspective that, because there are unknowns, literally anything could happen. And we don't think that's the case with my vaccines or code.
Pushing v2 of your webapp to master isn't going to cause rockets to launch. There are things that could happen and there are even very surprising things that are unlikely but could happen. But not everything is possible.
When we say "we understand how vaccines work pretty well", we mean that in the same was as "we know how our app works pretty well". That doesn't mean that we can't still be surprised, but it does mean that we have some things that we can be confident won't happen.
One such thing is sudden onset symptoms well after the thing has left your system, because there isn't a biological way for that to have an effect (to use the code analogy, you enable an experiment, it modifies database writes for a while, then you disable the experiment and delete the code. Once you've deleted the code, we know it can't do anything else, because it's not there anymore.
> One such thing is sudden onset symptoms well after the thing has left your system, because there isn't a biological way for that to have an effect
The hard part about conversations like this are that you could have written the definitive book on this stuff, or you could be just another dummy on the internet like me. So I have to take a statement like that and do my best to evaluate it myself, since I have no idea how to value your expertise. If you're an expert of some sort, I apologize in advance.
We know for a fact that vaccines have long term effects. They wouldn't be useful otherwise. It would be nice if they could only have positive long term effects, but why would there be any guarantee of that?
Symptoms could start immediately but be undetectable until they progress far enough (think a tiny little tumor for just one example). Again, not claiming this is happening, just saying that it seems nutty to assume it can't happen.
When I read "we understand how vaccines work pretty well", I automatically translate it to "we understand pretty well what happens when we inject a substance into a human body", and then I think "really?". We have some useful models, sure, but "understanding pretty well" seems a vast overstatement of the situation, especially when its laypeople chatting on the internet.
The abstract concept of a vaccine is pretty simple. Anybody can regurgitate the picture book version of it. Any specific instantiation of one is remarkably complex, all the way from manufacturing, to transport, to administration, and then interacting with the legacy ball of spaghetti that is the human body and it's various systems.
The fact that we humans decided to name some substance the same thing that we named some other substances that we created in the past doesn't necessarily tell you how that substance is going to interact with the body. It can provide you with hypotheses, but hypotheses need to be tested.
> We know for a fact that vaccines have long term effects. They wouldn't be useful otherwise. It would be nice if they could only have positive long term effects, but why would there be any guarantee of that?
Correct, but, and this is the important bit: the only lasting thing the vaccines do is leave your body primed to react to certain proteins (everything else they "do" leaves the body pretty quickly, you can think of this as a fairly limited api they're interacting with). This could be a bad thing, but if it is
1. Anyone who naturally caught covid would also suffer the same consequences
2. you'd expect to see the issues as soon as the immune system was primed, this takes days to weeks, not months.
So yes, there are all sorts of weird thins that could happen, but I'll reiterate: we know of know biological mechanisms that would make those things happen suddenly, without warning, months after the vaccine. We understand, very well, that such things can't really happen.
Just because you don't understand the human body very well doesn't mean the medical establishment also has equally no clue.
> the only lasting thing the vaccines do is leave your body primed to react to certain proteins
That is of course the goal, and assumes nothing goes wrong in the manufacturing, transport, or delivery mechanism for the payload. But if they haven't been tested for long term adverse effects, how do we know this? And again the answer ends up being because we know how vaccines work and round and round we go.
But let's leave that and assume that it actually does verifiably only prime the immune system to react to certain proteins. Is that some small thing? Immune disorders can range from annoying to horrific, and they're all from just reacting to certain proteins.
> This could be a bad thing, but if it is 1. Anyone who naturally caught covid would also suffer the same consequences
This seems to be a hypothesis. The current vaccines are based on a modified little chunk of a now extinct(?) variant of the virus plus some novel packaging. That they should have the same effect on the body as the whole current or future dominant variant (edit:
entering the body via a different pathway) doesn't seem obviously true.
> you'd expect to see the issues as soon as the immune system was primed, this takes days to weeks, not months
Why? I'll use the same example again. If a tiny little tumor were formed, or would be formed over time as a result of some protein reaction that started right after being dosed, why would you expect it to be detectable immediately?
The specific mechanism isn't important, it's just the "we can't think of a way it could fail, therefore we dont need to verify this" is just impossible for me to get my head around.
Feel free to drop the conversation if this gets frustrating. I will continue to ask until I understand, and I may not get there. I'm actually enjoying this, but I know I'm weird and this drives some people nuts.
> Just because you don't understand the human body very well doesn't mean the medical establishment also has equally no clue.
Fair, but that's not my claim. I can be at 1, while the medical establishment is at 100, and actual understanding of what's going on in the body could be 10000. We do some black box testing and get some somewhat repeatable results. That's a pretty amazing feat, but still a far cry from really understanding what's going on under the hood.
Comparing vaccines to software is an analogy I find very nutrient-rich. Basically, it can illustrate many points pro and contra, depending on what direction you're coming from.
Pushing webapp code to master certainly won't result in rockets launch, if only because no sane person physically connects launching platform to build server ("no biological pathway"). On the other hand, deploying build artifacts carries much more risk. This risk is usually mitigated by extensive multi-level testing and appropriate live monitoring. In addition, the target environment for software is, at least theoretically, fully tractable. I.e. it can be de-constructed and understood to the very last bit. It is also fully human-made and controllable, without random nuclear reactors hooked up to web server. If such invariants cannot be established, I think it is not ethical for a senior software engineer to approve mandatory wide-scale deployment. Under such conditions the decision must be strictly on the owner of each server.
In case of vaccine we deal with infinite number of reasonably unique "environments" - human bodies. We know that each of these "environments" are absolutely capable of developing a million of adverse things like cancers, strokes, autoimmune diseases, etc. So, the "biological pathway" exist, the "rocket launchers" are there. Our understanding of inner workings of human body is very imperfect, as demonstrated by the fact that humans still suffer and die from all sorts of diseases. Our monitoring tools are very limited, and our analytical framework is just blunt statistics. The vaccine is, basically, a clever hack into a half-understood system. So, it is certainly up to the owner of the body to decide what to "deploy" into it. And disagreement or misunderstanding, in my opinion, is exactly around the concept "who really owns one's body".
The database analogy is also interesting, in that while the experimental writing code is gone, the database remains modified. In sufficiently complex and poorly understood system how can one guarantee that modified data doesn't cause any unhandled exceptions down the track, especially given the number of vulnerable third-party clients?
Yes, what you wrote mirrors a lot of my thoughts and questions on this. These are the kinds of analogies that I can't help but draw when I hear the communications around covid, and there are never any satisfactory answers.
The thing to understand about vaccines is that they trigger things that your body does all the time by itself. A vaccine is more like kicking off a job than deploying new source code.
> The thing to understand about vaccines is that they trigger things that your body does all the time by itself
I'm not against vaccines at all for the record. But this doesn't seem like a strong argument for them.
Cells multiply by themselves all the time. Triggering that effect is how you get cancer. Your heart beats constantly. Triggering that too much (or in the wrong rhythm) is not a good thing. There are probably a ton more examples.
> Cells multiply by themselves all the time. Triggering that effect is how you get cancer. Your heart beats constantly. Triggering that too much (or in the wrong rhythm) is not a good thing.
Those are wrong analogies though. Vaccines don't trigger something too much. They trigger the exact same mechanism that will be triggered anyway when you get infected with the actual virus, but in a safe way.
I kinda think of it as if you were writing an unofficial third party client for a black box remote API that doesn't want third party clients and can update all their official clients in days or weeks in different ways.
Generally the long pole in vaccine approval is showing that it works - not that it's safe. If there's only a handful of cases worldwide, say for Ebola, then you have to vaccinate a few thousand people and wait for a period where a statistically significant portion would have caught the disease and then didn't. This can be years. There's only a few cases per year, you can't just give a bunch of people Ebola to see if the vaccine works. They're not waiting for 'long-term side effects' to show up, they know they don't exist.
However, with HIV as with COVID, there's a pretty significant installed base around the country so showing that it works isn't really a challenge.
Usually only a few thousand or tens of thousands of folks participate in basically any drug trial, btw. We very well understand the risk profile of mRNA vaccines at this point, having deployed billions of them and studied the technology for 40+ years. And having studied vaccines for upwards of 300 years.
I ask that you please speak to some people in South Africa or Botswana where almost 20% of the population live with HIV, including children (both victims of rape - there was and still is the belief that having sex with a virgin can cure AIDS - and children of HIV-positive mothers who were born with the condition).
It's beyond inhuman, and if such a vaccine were to work it would be as impactful as the eradication of Polio (yes, I know it still exists in some places) or Smallpox.
mRNA treatments likely will accelerate the trial process because their purview is so limited, compared to other molecule based treatments.
So more likely you’ll just get over a shorter release cycle and the longer one gets deprecated, relegated to certain style of treatment that mRNA based investment and research will run laps around anyway, further pushing people to evaluate and prioritize mRNA versions.
You can try to hold out for an arbitrary threshold of “long term” for your own comfort level. Its accurate that the state wont be helping you.
mRNA is like a file for a 3D printer, telling the body what to print for. Other styles of treatments were showing the body the payload. We will definitely learn how often we can get the body to do this, but I wouldn't call it an inferior beta status. Its just as good (or bad) as the longer process for different kinds of treatment. Same efficacy, which allows me personally to not focus on that.
I definitely don't have any knowledge on the topic. Here are my crackpot opinions:
1) Maybe many or most infected have a single strain each, and a targeted vaccine to each's strain could work as a treatment, similarly to the tetanus and rabies vaccines. Even if not a full cure, could be a way to halt the disease progression with lower cost and side effects than the current treatments available.
2) HIV spreads relatively slowly, so maybe flu-style annual vaccinations to at-risk groups for hot strains could be enough to actually revert the epidemic over decades.
Regarding your second point, isn’t HIV a preventable disease? In the areas where the prevalence is in double digits, people don’t seem to be using condoms or taking other precautions. Why would they be taking vaccine every year?
The vaccine wouldn't mess with sexual pleasure, something that hampers adoption of condoms. While condoms transmit pressure sensation just fine, the shearing sensation is diminished. Older men with mild ED may lose erection in the interval necessary to apply a condom. I believe there is space to disruptive innovation in the condom market.
I somewhat agree, but condoms aren’t just for HIV and save from other potentially lethal diseases. So the benefit is just enormous, yet folks still don’t use them. At the same time, look the vaccination rates in the Eastern Europe. I suspect it’s somewhat hard to get people vaccinated against the disease they don’t take seriously. I mean, HIV is horrible. Yet so many people ignore protection.
Why on earth do people get all uppity about the COVID vaccine requiring multiple shots? Basically every vaccine you've ever had (and you've likely had a lot) required 2, 3, 4 or even periodic shots for your entire life.
- Flu. Twice per year until age 9 then one per year, forever.
- Td, one dose every 10 years, forever.
- Tdap, 4 doses.
- Pneumococcal, 2 doses.
- Rotavirus, 2 or 3 doses.
- Meningitis, 2 doses.
- MMR, 2 doses.
- Hepatitis A, 2 doses.
- Hepatitis B, 3 doses.
- HPV, 2 or 3 doses.
- Polio, 2 doses.
- Varicella, 2 doses.
Seriously, we've had vaccines for 300 years. This kind of shocked Pikachu reaction to the very concept of a booster is tiring and adds nothing to the conversation.
Honestly, one dose every 3 months to avoid AIDS? In a heartbeat. How is getting an ouchie once in a while anything other than a remarkable scientific breakthrough in the prevention of one of the most insidious diseases we have?
> Don’t get me wrong, I got my 3 Covid shots. But that’s within 6 months. No other vaccine is that frequent.
That's not at all true, though the number drops pretty low when you eliminate the various series for infants that have doses at something like 2, 4, and 6 months (and often a fourth at 12-15).
But even eliminating those, there's a 3-dose/6-month HPV vaccine series, and a 3-dose, 6-month series for Meningitis B for populations at elevated risk, and maybe others.
I haven't looked into the Moderna vaccine but in general there are many ways to get rid of a virus. Using the typical B cell + viral glycoprotein is the most obvious way as viral activity is hard to detect when replicating inside a cell but there are many stages in the viral replication process which can be inhibited. Inhibiting protease cleavage of the viral polyprotein or preventing polymerase formation are all possible solutions. They don't really count as vaccines though.
>HIV mutates so easily. I understand the basics behind how mRNA vaccines are generated, but I don't understand why this approach would be expected to have any more success in evading the high mutation potential of HIV than other vaccine types.
you buy not an mRNA vaccine shot, you buy subscription. We already getting a preview of it with the 3rd, 4th, ... Covid boosters. Allowing for cheap and fast vaccine development the mRNA tech is changing the business of vaccination. Add to that that in near future you'll be able to get personally customized mRNA vaccine. You'll just be getting your monthly/weekly vaccine subscription box. And why limit to vaccines? The mRNA can make your cells produce any protein. Imagine a subscription business possible here.
If there's less spread of any given variant (because of vaccines), you indirectly decrease the chance of mutation no? A virus doesn't mutate outside a host.
Your comment insinuates a conspiracy theory, equating OP comment with theories of 5g causing COVID. It does not add much to the discussion and comes across as dismissive.
My experience is that as soon as we make a judgement call about someone, and put them in a pre-conceived box that we do agree with, we are unable to learn.
I went and re-read OP post.
nothing in it is close to what you are insinuating.
Yes there may be some unsubstantiated claims, or calling out faucci but shutting down discussions with comments like yours are unhelpful.
The video they linked contains a cherry picked selection of quotes from Faucci and presumably pharma execs about accelerating vaccine approvals and arguing that a pandemic would help with that.
Considering the rest of the comment and the throwaway account, yeah, for sure the comment was in conspiracy-land.
My comment was useless, yes. Flagging it was probably much more impactful.
Last I heard unless you can perfectly destroy it, any vaccine triggers a immune system response, which causes your body to bring more food right up to the virus.
If we can attack the spike protein of the virus, and it can't mutate around it, then the t-cells can still kill it vs just getting consumed faster.
> As I understand it, the reason an HIV vaccine has been so difficult to create is that HIV mutates so easily.
Nope. There are exactly two species of HIV since at least the '80s. HIV-1 and HIV-2. HIV however can trick the immune system into creating non-neutralizing antibodies, that can't fully prevent the progression of the infection.
If you run a large pharma company you probably already make a lot of money from long-term HIV/AIDS treatment. From the CEO's perspective developing a HIV vaccine may shrink the antiretroviral market if at-risk groups vaccinate themselves. Therefore you prioritize more lucrative projects.
HIV vaccine makes sense if:
1. You can hope for a general mandate of your product, or:
2. You are a small pharma company looking to make a name for yourselves.
Regarding the benefit of mRNA vaccines over non-mRNA vaccines for HIV, I don't know. I have yet to learn if there is significant medical benefit to mRNA other than reduced cost and TTM.
AFAIK mRNA does not enable producing new types of proteins, only this time they are produced by your body, right?
This conspiracy theory missed something important: competition. There are other companies with their own treatments either one the market or in development trying to take away your customers. If you can find a better treatment and roll it out you get all that money, if you don't you risk someone else finding it first and taking away all your sales anyway.
The more effective treatment will shrink the market, therefore market forces incentivize competitors to cooperate. It is the same reason that the OPEC exists. It is called game theory, not conspiracy theory.
OPEC is not terribly effective and suffers from constant bickering behind closed doors. The same motives apply - even if there was a "HIV vaccine cartel" there would be a massive incentive to undercut it.
I remember growing up being terrified of HIV/AIDS. The idea of something being permanent and transmissible via sex, and literally dismounting your immune defense to all other diseases on the planet...
To this day it still terrifies me, even though the treatments have become so good.
Each year it seems there are new stories about HIV research, and progress keeps being made. I pray for positive results and am really amazed. We have a lot to be thankful for.
Seriously! AIDS changed culture tremendously, and created a ton more fear around sex. If a vaccine is developed for it, it will be epochal -- like the introduction of Penicillin.
A cure for AIDS is almost like a cure for cancer, or fusion power. It's one of those technological miracles you thought maybe wouldn't ever come.
Or the Pill, or the Bomb.
(I know antivirals have advanced tremendously, but very few people would choose to be stuck on those. Also the progress was gradual enough that it didn't really affect straight peoples' consciousness. For most, AIDS remained a scary threat on the horizon, persistently uncured, still an eventual death sentence.)
So, this is wonderful news.
I don't think it will actually affect culture very much though. Straight people still worry about pregnancy. People are generally more cautious than they used to be. And the sexual counterrevolution is in full force.
But still. It'll be wonderful to close the chapter on AIDS. And it's inspiring that these long-term projects can eventually pan out.
Well if it is "that revolutionary" I'm convinced the modellers need to readjust their 9billion peak human lives estimate.
I think HIV is probably only one of the reasons the developed nations cared about pushing contraception in the developing world. If that fear rather than education goes I think some regions will see population explosions...
We must have started having sex at the time (90s?). Even as a straight man, who religiously used condoms (because being terrified), I was scared the first time I took an HIV test.
* Herpes vaccine - 10 different ones in development.[1]
* Hepatitis C - difficult, and several vaccines have been developed that didn't work.[2] Drug treatments are effective, at last, but started at $80,000 and are now down below $30,000 in the US.
Just to address this. There is no evidence anyone produced HIV in a lab and then released it, accidentally or not, out into the world. Scientists have established a pretty robust causal chain for where HIV came from. It is plausible that HIV was spreading between humans before we even really had the field of Molecular Biology that would have allowed us to “make” HIV.
I didn’t say it was not natural. I simply said it would not surprise me if it were not. It’s interesting how even asking a question about things can become taboo.
But you didn't ask a question, you made a statement. There are only two reasons I can think of for why someone wouldn't be surprised if something that is almost certainly false turned out to be true.
1. That person is wholly ignorant of the subject and so nothing about that subject would surprise them because that individual has no reason to believe anything about it one way or another. As an example, it wouldn't surprise me if it turned out that the Birch-Tate conjecture turned out to be false, because frankly I have no idea what that conjecture even means and so I have no reason to be surprised about it one way or another.
2. That person has expert knowledge about a topic that is not known by either the public at large or even by other experts in the field. Perhaps that person has devoted extensive and specialized research and managed to reveal a strong body of evidence that overturns the best commonly held understanding on that subject.
The reason I suspect you are being downvoted is because most people on HN think you're in category 1, that is you're someone who is not sufficiently informed on this topic to be surprised by it one way or another, and hence your comment comes across as revelling in your own ignorance.
If you're in category 2, then you have my sincere apology and I'd be genuinely interested for you to share your knowledge, but I somehow doubt that will happen.
Thanks for this :) Probably the best thing about the culture of science is that ignorance is often answered with polite explanation. Many scientists I know expect their own ignorant comments to be answered the same way. It is much harder to argue against a polite and well argued scientific response!
I merely said I would not be surprised, implying that I am not completely certain everything is as it is always commonly believed. If you feel the comment was dumb that’s your opinion and perhaps others share it but it’s hardly more than an opinion. I am quite aware of what real science is and what hurdles it has gone through for the past several hundred years to rid itself of political inhibition.
I wonder if we'll see HSV also addressed by this new wave of mRNA vaccines, or if it's just not top of mind for companies and researchers due to its "mostly benign" nature. At least until one's immune system starts to weaken with advanced age and it starts to cause all sorts of problems, but perhaps by then it gets swept under the "problems of aging" rug.
Dr. Friedman and team at UPenn are working on exactly this. An mRNA based prophylactic (and also potentially therapeutic) vaccine for HSV. I think they were originally using some other form of vaccine (a protein vaccine?), but then realized that mRNA was a lot better. He has posted a few video updates on the progress, and it looks good, but of course it hasn't entered phase 1 yet (supposed to start this year).
Yes there are multiple efforts with that one being I think the most promising. They hope to cure the first humans of HSV in 2024. I believe they have all the funding they need for now, having raised over $500k.
It's interesting how small some of those grants and funding pools are compared to what you see in startup land.
Maybe this is just the economics of viral research, but you'd think that with plenty of people out there willing to pay to cure themselves of HSV, or prevent it, there would be more financial support.
Yet, the people working on the problem have as much funding as the YC Standard Deal announced this month. I wonder why.
I feel the same way. So much money gets thrown around to solve relatively trivial problems, but I suppose it is like a casino where you hope to win. Whereas no one funding this research expects a financial return.
But you’d think that for example you could consider the tax payers as a body which would generally appreciate a cure to HSV. We could imagine the government funding such things. We just dropped an F-35 in the ocean in the South China Sea. I wonder how much research you could fund for the price of one of those.
I have an interest in this too, with most of the worlds population infected with some type HSV and being linked to Alzheimer's disease, MS and many horrible disease.
Epstein-barr virus is in that same category of “lots of latent, lifelong infections that are maybe linked to a ton of age-related diseases in weird ways”. No idea if it’s a potential target, but would be pretty cool!
Well just be careful. If the disease is caused by latent virus in the brain triggering chronic inflammatory response in the brain creating ROS that degrade brain maintenance mechanism (which is a reasonable hypothesis) -- creating a stronger inflammatory response might accelerate the onset of the disease, not prevent it.
I think we need to do a much better job at wiping out these "mostly benign" viruses. I suspect we'll someday learn they drastically increase your cancer risk, like we did with HPV and male throat cancer.
There is no shame in it, different diseases and viruses affect different people differently, because of different behaviors. It does not make Gay people worse, or better. It just means the actions they participate in, as a demographic cohort, is more likely to lead to an HIV infection when normalized for factors against another, non Gay, group.
HIV has always been a huge thing in the gay community, and erasing that or trying to shift from that is an odd form of historical rewriting. Anyone who lived in SF during the HIV epidemic remembers this.
Men who have sex with men are vastly more likely to get HIV, but account for a minority of the annual infections globally. [1] Sex workers and customers make up a larger percent of infections. Most HIV infections occur in women opposed to men.
I don't find the language particularly offensive, but I cant imagine them replacing LGBTQ+ in the sentence with sex workers.
Then again, this is a publication for lbtq audiences, not sex workers.
I thought so too and tried to check the sources, which were a mess. I was willing to give the benefit of the doubt and say they are probably in the ballpark
> This perpetuates the myth that HIV is mainly a problem for gay people. Can we change to another article, such as [1]?
But how is that a myth? The US Gov site [0] that is linked in the engadget article literally states that
> HIV continues to have a disproportionate impact on certain populations, particularly racial and ethnic minorities and gay, bisexual, and other men who have sex with men.
Fruther down:
> Gay, bisexual and other men who have sex with men (MSM)b are the population most affected by HIV in the U.S.:
> MSM accounted for 69% of new HIV diagnoses in the United States.
While I agree that the focusing only on LGBTQ+ as a group is not an ideal way to put it, there is no myth in claiming that gay/bisexual men are at the highest risk of getting it.
Indeed, but the numbers from the CDC suggest that "non-monogamous gay, and bisexual, men who engaging in unprotected anal intercourse" are a very large part of the community.
It seems to be an LGBTQ-focused website, so it looks to be doing nothing more than viewing things from the viewpoint of (presumably) its biggest reader base...
The source appears to be a queer news source, so that's probably the reason behind the focus. HIV is certainly a major concern for the queer community.
70% of new HIV cases are among homosexual and bisexual men [1]. If we assume that the incidence of homosexuals and bisexuals among men is 5%, that means that homosexuals and bisexuals are 14x more likely to get infected with HIV than the general population, or 44x more likely than a non-homosexual male [2]. While 44x is certainly not "exclusive to", I think it qualifies as "mainly a problem for".
And, it should go without saying, but let's hope this vaccine pans out!
[2] 14x is compared to the general population 5% of which is comprised by gay and bisexual men. If 70% of HIV positive people belong to a 5% group, and 30% belong to the 95% group, that's (70%/5%)/(30%/95%) = 44x is the relative risk of contracting HIV if you belong to the gay/bisexual group than if you don't belong
I'm a bit confused by the timing of this. Here's a press release from only a couple months ago, in which a Moderna partnership on an mRNA vaccine showed some benefit in macaques, but mostly in delaying infection (i.e. most macaques in the treatment group still got SHIV). Only two of seven in the treatment group actually remained uninfected. It sounded like researches wanted to refine and validate their protocol before moving to human trials.
> “We are now refining our vaccine protocol to improve the quality and quantity of the VLPs produced. This may further increase vaccine efficacy and thus lower the number of prime and boost inoculations needed to produce a robust immune response. If confirmed safe and effective, we plan to conduct a Phase 1 trial of this vaccine platform in healthy adult volunteers,” said Dr. Lusso.
I interpreted "If confirmed safe and effective" to mean that more animal tests would happen.
2 out of 7 macaques didn't get infected after 13 weekly (anally administered) exposures to SHIV. The other 5 averaged 8 exposures before infection took place vs 3 exposures in the control group.
That's actually pretty good at preventing infection - 28.5% avoided infection completely, with the remainder clearly having a much more robust immunity than control.
I mean, it seems like it did _something_ meaningful. But if you were part of an at-risk population, how promising would you really consider an animal trial that, for most treatment subjects, delayed infection by 5 weeks? Note, these animals had received multiple vaccines/boosters spaced out over a year before they were exposed to SHIV, i.e they spent 10x as long being vaccinated as they resisted infection.
Better than nothing. Maybe not enough for me to stop whatever other practices I'm doing to reduce risk, but it seems like a good shield in case one of those others fail.
E.g. one class of alternatives is PrEP which is very effective, well-tolerated in many patients, and depending on country, pretty affordable.
Oh, maybe for various reasons, regularly getting and taking pills is difficult for some populations, and a series of injections makes more sense? Subdermal injections for PrEP are also in the works and look like they would work for more than a year.
I would love there to be a really highly effective vaccine. But PrEP sets the bar relatively high for a vaccine to actually be an improvement, right?
Sort of. There are side effects, which might or.might not be bad for any individual. And of course you can forget to take daily medication. Can the vaccine be combined is an open question.
Last night I read this Nature review paper [1] and this history article [2] that describe the parallel investigations in both mRNA technology and lipid nanoparticle technology that ultimately led to the development of mRNA based vaccines. As we come up on Nobel Prize season, the second article is particularly interesting if you want to get a preview of some of the possible recipients.
Honest question: since making
mrna candidate vaccines is apparently so easy, would it be feasible to include mrna of multiple disease proteins in one vaccine? Is there hope for e.g. a general std-vaccine that covers all of the most common std's?
Yes. On the respiratory side Moderna already have a vaccine in development for quadrivalent flu, COVID-19 and RSV in the same shot projected for a 2023 release.
That would be a pretty damn useful vaccine for society. With a bit of luck and talent we might look back on these years as a turning point for how well we can suppress respiratory infection severity and spread.
I think that this might be a follow-on benefit of Operation Warp Speed which had a post a few days ago.
From that post, it seems like one of the benefits to Moderna (apart from a big cash infusion) was that Moderna had the science, but did not actually have the experience and pipelines of actually bringing a drug to a broad market. They did not have the experience and infrastructure for large scale human trials and for the large scale manufacturing.
Experience with creating, testing, manufacturing, and rolling out the Covid vaccines, were I am sure invaluable in helping Moderna become a "full-stack" drug company.
Very excited by this development and looking forward to (hopefully promising) results.
It will be wonderful if we can make HIV/AIDS something future generations will only know from history books.
Does anyone know if mRNA tech can be potentially used to cure food allergy in the future? I know that the pattern is to train immune system to recognize a foreign object and attack it but is it possible to train immune system using mRNA to not attack in certain cases? I did come across a paper from 2018 regarding potential use of mRNA to fight food allergy but I haven't come across any updates since then.
I am very not a biologist but I can't picture how this would work. Immunotherapy for food allergies, specifically peanuts, involves basically microdosing the allergen until the immune system chills out. mRNA wouldn't help there, even if you made a vaccine that exposed a peanut protein it'd have the opposite effect you were going for. If you took a different approach and expressed a protein that suppresses the immune response, then in just days when the mRNA degrades the effect would be lost. I'm sure we will get many miracles from mRNA tech but this doesn't seem like a likely one to me.
I am only moderately not a biologist, but this seems essentially correct -- vaccines are trying to address false negatives, but allergies are (in theory) caused by false positives. The mechanics of T cell training in the thymus for self/nonself discrimination are only partially understood, but any approach to rewrite antigen recognition would be (A) extremely risky, by potentially inducing massive autoimmune effects if anything went wrong, and (B) much more impactful for e.g. organ transplantation than allergic response.
The mRNA would actually code for the protein (allergen) so they would not need to be injected. The main advantage of mRNA tech is that you can use the same device to create an limited number of inoculations by simply providing blueprints and letting your cells do the rest.
From my understanding, the effectiveness of the vaccine is measured by monitoring - in the real world - how many vaccinated people of a group catches the virus compared with how many unvaccinated did: how would it work in this case? I guess it would just take a lot of years to come up with a good approximation.
But in order to have a good approximation of the effectiveness, we would need people to get infected. If I simplify, I would get vaccinated and stop using protection (i.e. condoms) during intercourse, but then I may catch it and end up living for life with HIV (contrast to COVID where you still have fairly reasonable chances to recover from). How would trials work for things like this?
Please correct me if I'm wrong, but I hope you see where I'm going with this.
Not sure what the issue is. Tens of thousands of people get HIV each year; all you need to do is give some of them the vaccine and see if those people get HIV as much as the people you didn't give the vaccine to.
People are already getting infected, we don't need to do anything for that to continue to happen.
Easier said than done. In 2019, the estimated number of HIV infections in the U.S. was 34,800 and the rate was 12.6 per 100,000 people. Consider that normal clinical trials are a few hundred people. Men who have sex with men are ~25x more likely to get HIV, so you are still looking at 1 in 3,000 per year. You are talking about some pretty huge trials here even if you are focusing on MSM only.
This will be Phase 1 clinical trials, ie they're mostly about side effects (and potentially dosage): ie they'll mostly check whether this will kill you / which dosage van be considered mostly safe. But at later trial stages, this will be one method to do this. Another and mich simpler one: you check whether the vaccinated people develop the antibodies you're looking for.
This is going to unfortunately suffer the wrath of their last flu jab being mislabeled for efficacy, safety and longevity.
I'm not saying it doesn't work it clearly does cut deaths but I think public option is starting to irrevocably sway based on regions which pushed it first. Not to mention the "reduces transmission by X" number keeps dropping with more studies and data...
I'm curious how trials like this work, in that if you engage in practices that leave you at risk of HIV infection, you really ought to use condoms or other prophylactic measures. Without telling people they no longer recommend such practices, I wonder how they get enough signal to prove efficacy.
> high-risk low-incidence diseases like this conducted
If you're asking 'how do we test the vaccine without _trying_ to give people HIV", one option is to give it to a lot of people, and record their outcomes over time.
But first you need to prove the vaccine isnt like, super toxic in humans. So you do animal analog tests, then a limited test on humans, aka "Phase 1 trials". A previous article summarizes:
> Moderna’s vaccines passed Phase I testing earlier this year, which involves testing for safety using only a handful of human volunteers. Phase II tests for a vaccine’s overall effectiveness, and with the move into Phase III, Moderna will be looking at its efficacy versus other prevention treatments currently on the market, such as pre-exposure prophylaxis, also known as PreP.
That article may be wrong. According to clinicaltrials.gov, they were still recruiting for the HIV trial and the target completion date is April 11, 2023.
While HIV is a relatively low incidence in the general population globally, there are some specific regions and subpopulations in various countries at much higher risk. In short, they mostly test HIV vaccines on young, single gay men in the West and young, single heterosexuals in South Africa, Tanzania, etc.
I guess the same as in diseases like tuberculosis. I’ve just read an article where they studied immune responses in recent TB infections. The authors recruited subjects from South Africa. I think it’s not that hard to get them to join the trials since payout can be quite significant where such disease are widespread, especially compared to Europe or North America. And some areas have just outrageous HIV prevalence. Just sample a hundred people and you get a decent sample size.
I am just speculating, but in many diseases like rabies and chickenpox you can give the vaccine after exposure to help the immune system fight the infection. It's because the period between exposure and symptoms is quite long, often more than a month for rabies for example.
HIV can stay in the body for years before developing AIDS. So you can actually recruit people that have been tested positive recently and have not developed the disease.
A LOT of really good science was funded over the last two years. It will be a while before it's all understood and integrated. It does give me a little bit of hope.
this was the real endgame of the vaccine mandates, force the whole world to participate in a trial of mRNA technology so that it could start being used in other profitable products.
Were previous vaccines at least as effective as not getting vaccinated? Ontario data is showing vaccinated getting infected at higher rates than unvaccinated. (3rd grahp)
https://covid-19.ontario.ca/data?fbclid=1
If that's the case, its more like a therapeutic than vaccine. Literally going out to get some sunshine is therapeutic.
I'm sure billion dollar pharma companies love that they can sell half baked products to this lower standard going forward.
At least for most other products you can get a refund for something that doesn't work half the time. In this situation you can't even sue if it caused you injury. Hope you don't support this corrupt fuckry.
It's important to remember that any community can spread it. Needle sharing among intravenous drug users comes to mind. However, you can't deny that HIV has struck a generational blow upon the LGBTQ+ community.
If this works it will be the end to an era of fear. Many will remember those that where lost and wish this only happened sooner. A new reason to celebrate is underselling the impact this will have.
It seems to me like lumping lesbians and the queer into this calculus is a little insensitive because it was almost exclusively gay men and trans women who bore the brunt. I'm sure this press release ran by a publicist who said, "we have to use all the letters or else we'll get torn to shreds on Twitter."
But on the other hand we are just talking about celebrating this. I feel like those sub-communities are probably more aware of the impact HIV than the average cis straight person and are probably going to celebrate this as well.
I don't get what's insensitive about it at all so maybe I am missing your point.
If we get down to brass tacks, this is a situation where sex takes precedence over gender. The HIV epidemic in the West was borne by XY people, and the history of HIV in America is by and large an XY history. What are we obfuscating by painting this history with a broadly "queer" brush?
It seems like HIV is mainly contracted by gay men in the First World, drug users in the Second World, and straight people in the Third World. It does seem a strange shoutout, but I imagine they are already prepping the ad campaigns for the West where they'll make the most money selling this vaccine.
It wasn’t just him saying that. I once went on a forum for a journal article, and there were two camps of biologists - those speaking about the similar sections, and those refuting the claims. I noticed that most of the refutations came from scientists with Chinese sounding names. I realize that this is just anecdotal, and you can choose to believe me or not. But that’s what I saw.
You may still be able to find it on Google.
Also, from the first para of his Wiki page:
During the COVID-19 pandemic, Montagnier promoted the conspiracy theory that SARS-CoV-2, the causative virus, was deliberately created and escaped from a laboratory. Such a claim has been refuted by other virologists.[6][7][8][9] He has been criticised by other academics for using his Nobel prize status to "spread dangerous health messages outside his field of knowledge".[10]
Looks like he’s been at least partially vindicated.
I can see that you are not here to learn. So my replying to your comment would only be a waste of my time. For anyone else reading, I would direct you to recent research on the lab leak theory, as well as gain of function research conducted at that lab.
I remember headlines saying that, but the most I'm finding is that the paper that claimed such links was quickly retracted from bioRxiv[0]. I'm a bit lost as to how misinformation played in placing a Nobel Prize winner in the mix, possibly they mentioned there was research suggesting that link.
Sadly, given that it's a new (throwaway?) account used to post in a thread about a vaccine, there's a high chance this is another neo-anti-vaxxer, here to tell us why this is "not a vaccine" and all that.
I am just making a couple of considerations about you, audience, considering I silently read what you comment for years already. This is not a throwaway account. I just felt the need to express my opinion, if you are sad about that, and the only way to answer me is to label me as a "neo-anti-vaxer" you are just demonstrating my point.
But see, you didn't actually make a point in your original comment. I don't mean that rudely. You referred to the "arrogance [we] likely use to discuss the correctness of [our] code." What are actually saying here?
If you want to engage in discussion, I encourage you to use plain language. Accuse the community directly of whatever charge you're bringing, and then we can debate.
Would you deploy in production a software (which lack of safety could be critical) without being sure (or have proof) if it will effectively work as expected in 1+ years?
Would you be relaxed being the administrator of such a software?
All the manners in which the vaccine could have been tested, were employed before deployment. The only thing that wasn't done, as you note, is to wait for XX number of years to see long-term side effects. So in fact, we don't know what the effects of this vaccine will be in 10 years -- because the only way to know that is to wait 10 years. But... there is also no indication, from similar vaccines, that "something terrible" happens in 10 years.
A lot of people out there are just imagining, out of nowhere, than in 10 or 20 years, everyone who got the vaccine is gonna get autism or sprout a third nipple or keel over dead. But they're just imagining this. I can imagine a lot of things too... like, who here can prove to me that the new Doritos flavor introduced last year won't trigger brain cancer in 20 years? Anyone??
That is fine if you think things would have worked out better if we just treated Covid like another strain of the flu. 99% of ER Doctors disagree with you. If you think their opinion doesn't matter, that is fine too, but I don't see why I should ignore their opinions and agree with yours.
Industries cannibalizing themselves through competition is very common.
If pharma was a monopoly, then they wouldn't want to cure cancer. But pharma isn't a monopoly, so the incentive then is to reduce the size of the pie as long as they get to eat the entire pie themselves.
The conspiracy theory always ignores that cancer is a broad category. There will never be a single cure, but rather many individual cures. And the cures will really be more effective treatments that achieve remission very reliably. Most cancer treatments are already hypothetical cures, if things go well enough. The trick is to greatly increase how often it goes that well.
So you think everyone working in the medical and pharmaceutical fields is an utterly amoral antisocial personality disorder case? Because that's what it would take for your conspiracy theory to work. If you honestly can't understand compassion, well...
You are wrong. mRNA covid vaccines don't "only work for 90-180 days". First of all, you need 3 shots to get fully vaccinated in the first place. This is one shot more than the original approved plan, but a very common thing about vaccinations. I got 3 measels shots for example. This has to do with how the immune system works, repeated shots cause different effects which lead to improved immunity.
Also, we are facing very different variants. With the original strain and the first variants, the vaccines would have done their job with just 2 shots and we might even have achieved herd immunity. But delta and especially omicron did happen. Still, with 3 shots, the vaccines against the first strain are still excellent in protecting against severe disease and there is no indication yet that this protection is dropping significantly over time.
To stress this: we are talking about effects due to the nature of the human immune system and the virus mutations. There is no indication what so ever, that the mRNA technology produces shorter lasting immune responses. Quite the contrary, the mRNA vaccines are the ones which proved the most efficient against SARS-Cov-2.
If you are exposed to COVID but got the vax a year ago, you’re likely to have symptoms. You probably don’t actively have antibodies. But that’s okay! You might have some symptoms, in fact they might be severe, but given enough time your immunity will ramp back up, and you still will clear the virus.
If you clear HIV after a week or two, that is a HUGE win for you.
I don't know anything about vaccines or their validity, but even then, the current solutions are a shot once a month or PrEP every day... so twice a year sounds pretty great to me?
if someone has HIV, they can be treated and if they are consistent with treatment they can have such a low (undetectable) viral load that it is not transmittable. (aka U=U)
additionally, high risk populations (transactional sex, msm, intravenous drug users) can take the same drugs and be protected from the virus. (aka PREP)
also people with known exposures or likely exposures can have post exposure prophylaxis with the same drugs (e.g. in the case of an accidental needle stick in a healthcare worker).
These defenses have already radically slowed the spread and increased the lifespan and quality of life of those who become HIV positive.
Now we will hopefully have a an additional defense that will be even easier (no daily dosing required for negative at-risk population) and probably much more broadly administered.
No one in this thread knows anything about vaccines or infectious disease. Each organism is different and requires a detailed understanding to see what the potential for the vaccine is. You can't just take COVID-19's performance and project that onto another disease. mRNA allows the targeting of specific proteins. The efficacy of the T-cell and B-cell responses are going to be highly dependent on that protein's structure, its importance and level of conservation in the pathogen, and other factors.
COVID-19 seems to require a persistently high level of neutralizing anti-bodies and the T-cell response seems to be less important (and also plays a role in auto-immunity). On the plus side, the wild-type vaccine has continued to be fairly effective against even highly mutated Omicron which is surprisingly good even if strategically, it is suboptimal that the virus has continued to mutate and evade the vaccine to ever greater degrees.
…or it totally could, if it primes T-cells to fully clear the infection, or keep it to such a low level that the viral load is minimized.
HIV has a tremendous latency period. It lurks for a long time before symptom onset. If a vaccine doesn't provide sterilizing immunity, but does prime T-lymphocytes to clear the virus, or keep it to an extremely low viral load, it would make people substantially less likely to spread the virus, or have symptomatic progression to AIDS.
Not sure why you’re being downvoted all much… well actually no it’s pretty obvious.
I think you’re right though. The current Covid-19 vaccines are proven to lose efficacy over time. Will the same thing happen with this one as well? It’s a good question.
I think it's just the speed at which it has happened though. Most children born in developed countries today receive a slew of vaccines which will provide immunity to catching those diseases for decades. It's discouraging that we're looking at shot no. 4 for the mRNA covid vaccines within a year and a half, and despite even that, infection rates are still very strong.
Because corona viruses are a different kind. There have been no vaccines against them so far and we saw how strongly they mutate. Still, the 3-shot regime seems to be very effective against severe disease. They probably deliver as much protection as possible unless you have a vaccine which targets exactly the strain you are fighting. So it will be interesting how the omicron-specific vaccines will do, if they do get used for larger campaigns.
Thanks for the breaks analogy, it’s one I intend on using when talking to people I. The real world. It’s a good one given how basically everyone has either dealt with or understands this basic yet essential car maintenance issue and the nature of the appropriate response.
At least they don't make them from asbestos anymore.
My dad tells me about taking shop class in high school, and they'd be sanding down asbestos brake pads with an angle grinder to remove the high spots to prevent glazing. No masks of course.
OEM might not be asbestos but aftermarket asbestos containing pad can be bought. Who knows that the material does that's in them today?
I'm generally surprised by what I was exposed to at shop class, not necessarily asbestos but machines that could absolutely wreck a body let loose by a bunch of haphazard children. Blinding lights, kids sticking like 4 inches of iron into a hydraulic cutting machine and hitting go. A girl cut her finger off on a bandsaw.
because the point he's making is wrong. Vaccines are doing a fantastic job at slowing down the progression of the virus which is key to keep mutations at bay. No vaccine is 100% effective, but even 80% effectiveness radically changes the dynamic of a pandemic, it's so easy to see that I don't understand what can lead someone to deny this fact besides bad faith.
I think you may want to revisit your 80%. The vaccine efficacy for sterilization of the virus ended up dropping more quickly than expected and that's even with pre-Delta variants. Look at the Israel data. When you don't understand, I suspect what you are encountering isn't bad faith actors, but more informed people.
But here you're talking about efficacy against infection and mild disease, which is not so relevant if we're talking about preventing new strains. New strains are thought to evolve in immunocompromised people with high viral loads over long periods of time, which allows both many mutations to occur as well as for those mutations to become dominant. So I believe the question should be to what extent the vaccines help prevent serious disease in people with comorbidities - and the answer is that they help to a great extent (whether 70% or 90%).
I seriously doubt it. Show me your "israel data" and tell me how that changes the situation, because I don't believe you and you come with nothing but name calling.
Exactly. The COVID vaccines have been proven over and over again to reliably prevent serious illness across the original strain and every variant of concern we’ve seen since then. The fact that they initially also largely prevented infection against the original strain was a bonus that scientists were never counting on.
Now, just because omicron is better at driving breakthrough infections, that fact is being used in bad faith by some who now say the vaccines “don’t work”, even though they are still as effective at preventing serious illness
I wholeheartedly agree, I downvoted the comment because it appeared to be made in bad faith (and from another comment I posted on this topic, I obviously share the concern that this HIV vaccine may lose efficacy over time).
Also, it's not hard to see how a vaccine for HIV would be much more effective at slowing pandemic progression than a vaccine for an airborne virus, even if the vaccines conferred the same benefits. Right now, if you get HIV, you are essentially contagious for life until you get on antiretrovirals that can bring your viral load to undetectable (and, you also need to be on those antiretrovirals for life). If an HIV vaccine prevented you from having a long term infection, it could potentially fully end the pandemic.
There's a difference between "someone" and "no one" and "everyone". Someone with an engineering education should be able to understand that very easily, it's a shame you don't.
The Covid-19 vaccines were made against the original strain in which it was 95% effective. Let's see how the updated Omicron vaccine goes. I am guessing we are going to see above 90% effectiveness. mRNA vaccines are looking pretty promising at neutralizing the specific virus they are targeting. How effective that is for mutated and related viruses is what remains to be seen.
Wouldn't it depend more on how well-chosen the target protein is? If it mutates too fast the vaccine won't be as effective. This says nothing about the effectiveness of the mRNA technique though, which seems to reliable induce an immune response to the target protein.
PREP already gives you good prevention for this to work it needs to be both a therapeutic vaccine at least at stages at which PEP is no longer effective as well and or as being at least as effective as PREP whilst being more cost effective as an overall treatment.
Also there is no chance that this would have a higher adoption rate than COVID unless it turns out to give 100% life time immunity and would end up being part of the National vaccination program world wide.
This likely would have the same usage as PREP/PEP today so at risk individuals and a post exposure treatment.
what makes you think so? how could the market for this be greater than the market for the covid vaccine? the number of people susceptible to covid is much greater than the number of people susceptible to HIV.
but surely more people would say "my lifestyle choices mean that I'm never going to be exposed to HIV so I don't need a vaccine for it" than ditto for covid?
sure but the set of all people who engage in frequent unprotected sex so as to be possibly susceptible to HIV is strictly smaller than the set of all people who could be possibly affected by covid.
I'm not sure how we're lost in translation here, so I'll try to express this another way.
I think the majority of sexually promiscuous adults aren't particularly concerned about COVID infection, because the likelihood that they'll die from it is low. If they do catch it, they will most likely recover without long-term damage.
I think those same adults however are indeed concerned about HIV infection, because it is [so far] incurable, and has an enormous social stigma attached to it, and without constant treatment will eventually kill you.
The number of people who would benefit from a drug against COVID is larger than those who would benefit from a drug against HIV, however, of those who would buy either drug, I think the latter drug is the one that would have much higher market demand because of just how consequential an infection with that disease is.
well, hopefully that market demand results in getting a drug that is more than adequate at what it's supposed to do, because I'd imagine the consequences would be much worse.
I would be really worried with false sense of security when dealing with HIV/AIDS... Covid in the end is a mild thing, same can't really be said about HIV/AIDS. And if the protection is only temporary and partially it might be worse than having nothing at all if it leads to lot more risk taking.
Why did you get flagged when you are absolutely correct. Why would you think that mRNA vaccines, which failed for so many years in testing, would presto work this time. and they clearly didn’t work this time, unless you drone around mumbling how thank god your symptoms would have been worse without it.
As a matter of fact, the “trials’ during warp speed were so flawed to show efficacy it is pathetic. But these tech geeks here know better.
The covid-19 vaccines were very effective at preventing disease and spread until the omicron mutation, which perhaps wouldn't have happened if not for vaccine hesitancy. (but that is an inevitable human nature thing, so you have to accept it and deal with)
Fortunately the vaccines were still very effective at preventing death and hospitalization with omicron, I wonder how many lives were saved overall, so far? It is really quite remarkable.
Given the slower way HIV spreads we have a much better chance at actually getting rid of it. Its not flying around in the air mutating in a billion people at once every day.
Come on, this isn't true. Even with delta the waning efficacy had become obvious in those countries that vaccinated early, with all time high infections in jurisdictions that were virtually completely vaccinated (e.g. Israel, Waterford). One study estimated 211 days until protection vs infection was statistically indistinguishable from someone who was not vaccinated (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3949410).
And how can you possibly speculate that a vaccine evasive mutation is the fault of the unvaccinated? While we can only guess, the evolutionary pressure is obvious: a vast number of hosts available to the first variant that can defeat the narrow immunity against the spike protein. We created a monoculture, with all the attendant risks.
As much as I'd like to blame them, the number of people who willingly refused the vaccine are irrelevant compared to those who do not have access to it.
HIV doesn’t mutate in the same way a disease like Covid does, at least not at the same speed— also, PrEP has existed for years. It’s still proven to be effective protection against contracting HIV even if directly exposed (though it’s a pill that must be taken every day rather than a vaccine).
I honestly don’t know why everyone who is sexually active isn’t on PrEP (the federal government even mandates it be free to those without insurance in most cases)— it should be as common practice as wearing a condom and birth control, yet its existence isn’t even known to many people (especially among straight people).
This is a valid point, but I think ignores amount of public health resources "spent" on trying to address vaccine hesitancy and healthcare resources addressing "unnecessary" hospitalization and complications.
Now imagine we could cut the above in half, and then use some fraction of those savings (as a nation) promoting wider adoption of vaccines globally. If we've reached higher levels of vaccination earlier (in the USA), more people without access to the vaccine currently would've been able to get it.
My GF and I, both Moderna double vaxxed, were exposed to Covid last year. Same place, same time, she got it, I did not.
I still quarantined the whole time but not a sniffle, no fever, multiple negative covid tests for myself.
If the HIV vaccine works, some people will still get HIV given enough exposure at just the right time, for instance, undergoing cancer treatment notoriously wrecks your immune system, so you might be at risk even with a vaccine then.
You can still get the mumps and measles and everything else you've been vaccinated against given the right circumstances, but you do have far more protection against it than without the vaccines, and in an ideal world where every person was completely vaccinated and any sources of animal to human exposure were eliminated, then should your immune system suffer a setback there wouldn't be anything around you to take advantage of your weakness.
That is what herd immunity is, which was never supposed to be "if 90% of the population is vaccinated then the other 10% are safe" (which is a whole different story).
... and yet the HIV virus is notoriously terribly difficult to develop a vaccine against. It mutates easily and you don't have a natural antibody response that is easy to trigger. Like one of the top comments I really wish some expert would enter the discussion and explain what exactly are our expectations.
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The covid-19 vaccines were very effective at preventing disease and spread until the omicron mutation, which perhaps wouldn't have happened if not for vaccine hesitancy.
I'm happy to piss in the coffee of vaccine hesitants any day of the week (point me to the mug), but we can't blame the variants on vaccine hesitancy.
Both delta and omicron originated in unvaccinated populations in the developing world, where the problem is not vaccine hesitancy [1], but the lack of availability of vaccines [2].
[1] Delta arose before any vaccines were approved, and yes, of course, there's vaccine hesitancy in South Africa, but there's also, simply put, not enough vaccines to go around.
[2] For some mysterious reason, our economic planners thought that getting the developed world inoculated in 2021, and the developing world in 2022 was a smart plan. It wasn't, but now we're reaping the consequences of it. I eagerly await the next variant.
Please many countries like Israel were lit up with delta after being touted as the poster boy for “vaccinations” in June 21. Stop the nonsense. The data is clear, the effectiveness diminishes after 3 months. You can’t vaccinate your way out of a pandemic with pathetically leaky “vaccine”
But, HIV mutates super easily, which is why we do not already have a more traditional vaccine that works. It will be a greater challenge in this regard than COVID-19/Omicron, not an easier one.
1. Given the continued efficacy of the COVID-19 vaccines against severe illness, it stands to (lay-)reason that a similar outcome might occur with HIV. A world in which HIV is roughly as transmissible as it currently is (and is still responsive to other avenues of treatment/prevention, like PrEP) but where it does not cause fatal immunocompromization is an extremely preferable world.
2. We have no particular reason to believe that HIV's mutation vectors are more or less susceptible to the vectors that mRNA vaccines target, versus "traditional" vaccines.
Can someone with more knowledge explain the thought process behind this?