Moderna’s HIV vaccine has officially begun human trials | Hacker News Reader

Moderna’s HIV vaccine has officially begun human trials

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1,049 pointsgrawprog449 comments

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.

https://www.aidsmap.com/about-hiv/faq/what-elite-controller

And undetectable === untransmittable. Just in case people here didn't know.

> And undetectable === untransmittable. Just in case people here didn't know.

In no way saying this is not a good thing, but do we know if this can be sustained for the whole lifetime?

Or is it that 20, 30 years later, as people get older the person eventually gets AIDS?

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.

https://www.aidsmap.com/news/mar-2020/yes-same-life-expectan...

I've heard HIV patients describe ART as "aging" their organs. obviously preferable to dying horribly from AIDS, but still gnarly to contend with.

it's really interesting to me that their health becomes poorer earlier, but that it doesn't affect mortality.

I didn't know this. Could you explain the reason?

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.

https://en.wikipedia.org/wiki/Viral_load

https://en.wikipedia.org/wiki/Minimal_infective_dose

https://en.wikipedia.org/wiki/Management_of_HIV/AIDS

https://en.wikipedia.org/wiki/Viral_load_monitoring_for_HIV

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.

https://royalsocietypublishing.org/doi/10.1098/rspb.2009.006...

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.

https://www.cdc.gov/hiv/basics/livingwithhiv/protecting-othe... https://www.nejm.org/doi/full/10.1056/NEJMoa1600693#t=articl... https://pubmed.ncbi.nlm.nih.gov/27404185/

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.

So some other points.

Some Sex lubes can make it easier for infections to get into the body. https://en.wikipedia.org/wiki/Personal_lubricant#Water-based

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.

Presumably the viral load required for transmission is greater than the viral load required for detection.

My guess is it is more of a probabilistic thing than a strict threshold.

I mean just based on the definition that seems like the literal meaning to me. But i'm not a PHD

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?

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.

https://www.hiv.gov/blog/science-validates-undetectable-untr...

No detectable virus means no transmissible virus.

To reiterate the question, why is that?

False. Detectable is an experimental limitation of a given measurement system. Even one single virion can infect a host.

It depends on if your body is able to detect it better than a machine…

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.

Anybody remember hearing something like this?

> "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.

I wasn't contradicting you, I was adding more specifics.

That sounds fascinating. Got any links or search terms?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4136306/

Awesome.

Thank you! Just the kind of explanation I was looking for, most appreciated.

The IAVA press release discusses some of this:

https://www.iavi.org/news-resources/press-releases/2022/iavi...

Sounds like the mRNA platform is being tested as a delivery mechanism for immunological work that was done separately.

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.

mRNA may make a huge difference here.

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.

I’m not familiar with vaccine tech. Can’t you grow the peptide of interest and package it in a traditional vaccine?

> 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.

When you wrote <<sHIV>>, did you mean <<Simian immunodeficiency virus (SIV)>>?

Ref: https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus

No, I meant sHIV or SHIV, which are a family of human-created viruses with SIV structure and HIV sequences within.

https://journals.asm.org/doi/10.1128/JVI.00372-19

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 pretty sure that if the this vaccine succeeds there's going to be a new strain of HIV that can get around it.

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).

Something I learned today: PrEP also works "on demand", so for some people it may not be necessary to take it every day.

https://www.aidsmap.com/news/jul-2020/demand-prep-highly-eff...

> ...sort of like a morning after pill (but every day for a whole month).

Does this mean that there is a cure, but it only works if taken shortly after exposure (and 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).

Not a cure, as that implies recovery from a full infection. It's preventing your body from becoming fully infected.

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?

http://www.medicalnewstoday.com/articles/82330.php

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936006

You know, let me link the whole Wikipedia article on this very topic: https://en.m.wikipedia.org/wiki/Promiscuity#Gay_men_(homosex...

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)

https://www.independent.co.uk/life-style/health-and-families...

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.)

More about "seropositive": https://en.wikipedia.org/wiki/HIV-positive_people

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...

It depends on the sexual activities undertaken.

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).

The CDC has data at https://www.cdc.gov/hiv/risk/estimates/riskbehaviors.html

Long story short, it's probably not worth it for most people unless they're engaging in unprotected anal sex with people who have unknown HIV status.

>a lifelong illness

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.

I see the point but you could argue the same for nicotine dependence, diabetes, depression & anxiety, vision problems, allergies, etc.

Maybe you can't afford the treatment, maybe you have side effects, maybe you don't know you need it...

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.

Discovy is not, or much less so.

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."

https://twitter.com/scrippsresearch/status/13581208549709127...

Direct link to video: https://www.youtube.com/watch?v=BrmXpMmvHWw

This explains the background on broadly neutralizing antibodies that the other commenter `mlyle` mentions. Worth the watch.

I am not an expert, but there has been a lot of hope recently that because we have much better understanding of protein structure (e.g. https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi...) and because mRNA allows us to tightly control the genetic sequence, there is hope we could target some part of the virus that _is_ well-conserved across variants. e.g.: https://pharmaceutical-journal.com/article/feature/preventin...

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.

CureVac did not have any pseudouridine modifications. This is relatively easy to do and I’m not sure why they did not do it.

> 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?

By that time, I'm sure they will have switched to the monthly subscription model. Unlimited vaccines anytime you want only $9.49 month*

*when paid annually

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.

> They are fast to develop. However, there are other steps in the pipeline that aren't so fast.

It doesn't seem meaningful to define development time without including all the steps required to provided an available vaccine to the public

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.

> and maybe to Chimp Adenoviruses

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.

I wouldn't call it arbitrary sequence, it's a specific sequence ie. s protein for covid.

Saying that, it's now a known cause of blood clotting in some recipients: https://www.science.org/doi/10.1126/sciadv.abl8213

"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.

> The traditional vaccines don't work any better.

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:

Omicron: https://www.pfizer.com/news/press-release/press-release-deta...

Mentions delta: https://cdn.pfizer.com/pfizercom/2021-07/Delta_Variant_Study...

Yes, but what I meant was those would be already approved.

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.

The yearly flu shot is composed of preexisting vaccines, they're not developed anew each year.

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.

What's the rationale behind your assertion?

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.

I think slowly will come the realization that mRNA vaccines aren’t as fast to develop as people thought.

It took 2 days to develop the vaccine. https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19...

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.

If we had robust enough theory of vaccine testing it wouldn’t matter what kind of vaccine you develop, right?

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.

Maybe, maybe not? Mrna vaccines are very customizable so they could be specifically engineered to avoid known safety issues for example.

If we can do it this fast and this safely for COVID, we should do the same for this disease.

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.

> The slow part is the safety testing right?

No, the slow part is the efficacy testing.

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!

What I’m trying to say is that mRNA vaccines might not be faster to deliver to market because you still need to go though testing and approval.

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.

As I understand it delta boosters have been tested, but were not more effective than a normal booster.

Omicron has only been discovered in November and booster trials are still ongoing.

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.

Another reason the vaccines didn't stop the virus is that not enough people got vaccinated.

> The newspapers never should have sold vaccines as a way to stop the virus in its tracks.

Which newspapers? It's easy to take shots at 'the media' (or equivalent).

Well it wasn't virologists or epidemiologists.

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.

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.

We get a new flu vaccine every year, is this much different?

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.

Works great with the sars-cov-2 vaccine so far. That's why there are fewer symptomatic infections since the vaccines are out. /s

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.

There are far fewer symptomatic infections and deaths than there would have been otherwise.

> 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.

https://www.pfizer.com/news/press-release/press-release-deta...

https://ir.novavax.com/2021-12-22-Novavax-Announces-Initial-...

> No, it wasn't

I said "for Delta". If you read the rest of my comment I mentioned the upcoming Omicron vaccine too.

> 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.

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.

getting a shot once a year is way easier than a very expensive pill every day (prep) or even using a condom every time you have sex.

It's a lot easier to get folks to agree to one or two shots one time than to convince them to change their sexual practices, one would imagine.

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.

Is this related to the concept of original antigenic sin?

so everybody gets it soon?

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.

You're gonna need a citation or two for all of that.

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.

Religiously using condoms is not using them very much

Honestly, the fact that 4 STDs are incurable still frightens me.

HIV, HPV, herpes, what’s the fourth one?

At least for HPV there’s a vaccine though.

* HPV vaccine - in use

* 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.

[1] https://www.precisionvaccinations.com/vaccines/herpes-vaccin...

[2] https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8402855/

Hepatitis C. Although there's a cure for a large percentage of cases, it's still not a cure for everyone.

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.

More details on this subreddit and specifically this sticky: https://www.reddit.com/r/HerpesCureResearch/comments/kg66ds/...

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.

Vaccines and cures deliver one time revenue, whereas treatments deliver perpetually recurring revenue. It's a well known market failure in healthcare.

Yeah, after seeing game studios being bought for 64B dollars, how many HSVs could that cure?

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.

It's about time we defeat HSV too!

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!

Ask and you shall receive:

https://www.umassmed.edu/news/news-archives/2022/01/phase-i-...

Very 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.

The them.us article [0] says:

> but we’ll be praying ... that by next year, LGBTQ+ communities around the globe will have a new reason to celebrate.

This perpetuates the myth that HIV is mainly a problem for gay people. Can we change to another article, such as [1]?

The Bill & Melinda Gates Foundation supports Moderna's HIV vaccine research [2].

[0] https://www.them.us/story/hiv-aids-vaccine-human-trials-mode...

[1] https://www.engadget.com/moderna-mrna-hiv-vaccine-trials-225...

[2] https://www.modernatx.com/ecosystem/strategic-collaborators/...

I don't understand how a fact is a myth?

https://www.reuters.com/article/health-global-aids/men-with-...

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.

https://www.avert.org/global-hiv-and-aids-statistics

The pie chart in your link seems a bit suspect, there is a lot of overlap with the groups included.

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.

[0] https://www.hiv.gov/hiv-basics/overview/data-and-trends/stat...

This number changes dramatically when you look globally. MSM is about 23% of new infections

https://www.avert.org/global-hiv-and-aids-statistics#footnot...

Because it include subsaharan africa globally. Readership for this site is probably only in United States and here it is mostly gay men

More like it perpetuates the myth that LGBTQ+ is a monolithic group.

HIV is more concerning for Gay men for a variety of reasons. There is nothing wrong with pointing out the obvious. Ask anyone who takes prep.

Your comment perpetuates the myth that gay men as a group are a homogenous whole.

More specifically HIV, it's more of a concern for non-monogamous gay, and bisexual, men who engaging in unprotected anal intercourse.

That seems like it's needlessly splitting hairs.

"STDs aren't a problem for humans as a group. They're a concern for people who have sex"

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...

It really isn't a myth though [1].

[1] https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/cdc-msm...

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!

[1] https://www.cdc.gov/hiv/group/msm/msm-content/incidence.html

[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

https://www.cdc.gov/nchhstp/newsroom/docs/factsheets/cdc-msm...

I'm a gay dude and see nothing wrong with that statement.

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.

https://www.nih.gov/news-events/news-releases/experimental-m...

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.

But the alternative isn't nothing.

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?

https://www.cdc.gov/hiv/risk/prep/index.html https://www.aidsmap.com/news/mar-2021/reformulated-islatravi...

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.

I’m curious how that compares to PrEP but I suppose both would be better than one.

"PrEP reduces the risk of getting HIV from sex by about 99% when taken as prescribed," according to the CDC: https://www.cdc.gov/hiv/basics/prep/prep-effectiveness.html

It’s hot tech, maybe driven by the desire to pump share prices.

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.

[1] https://www.nature.com/articles/s41578-021-00358-0 [2] https://www.nature.com/articles/d41586-021-02483-w

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.

Why is the comment with the actual press release that honestly gives far better info flagged to death? @Dang can you fix this?

Interestingly their five link submissions are all dead as well. I'm guessing it was some kind of automated response based on the account history.

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.

https://www.hiv.gov/hiv-basics/overview/data-and-trends/stat...

This info should give you a better idea of how one might compose a set of trial groups for something like this.

Thank you, this is a good resource!

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.

Absolutely no issue. I was just wondering how we would possibly approach it. And got my answer! Thanks.

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 an even bigger deal than COVID vaccines. Many third-world nations struggle hard with HIV/AIDS; this can be revolutionary for them.

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.

I assume they will test it in regions of the world that are more affected

So all it took to get here was €10 bln from EU governments and $10 bln from the US government to push the rapid development of mRNA tech?

Shouldn’t this be done regularly? How about $20 bln to finally get a good malaria vaccine?

Don't worry they'll have Africa sign a contract saying they can't sue when it turns out to not quite work as it's hyped to to.

How are human trials on high-risk low-incidence diseases like this conducted?

> 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.

- https://www.them.us/story/moderna-begins-hiv-vaccine-trials-...

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.

https://clinicaltrials.gov/ct2/show/NCT05001373?id=NCT050013...

Edited because my previous version was possibly wrong.

Okay, well, it still outlines clinical trial phases correctly, right?

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.

If a HIV vaccine really is happening, that will really brighten the memory of the last two COVID years.

And as always there are some great insights to the inner working of the vaccine, Hacker News doesn't disappoint.

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.

I thought we would never find cure for HIV. This is such huge news.

I have a friend who has HIV with a zero virus count.

Does anyone know if this will combat the latent virus?

From what I've read, no. Once you're U=U, it seems like no treatment can rid the virus completely.

I would love to be corrected though.

Thanks for info. Thats expected. Just wanted to check and be sure. I know dealing with the latent HIV has been a big challenge.

I would never put anything made made by Moderna in my body even if I was on my deathbed.

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.

It's a good thing they didn't mandate that you get an mRNA vaccine .

Will you still be able catch HIV and pass it on to others all the same, with "lesser symptoms", until the day you die from HIV?

The post 2021 changed definition of "vaccine" is a bit of any oxymoron.

What change? Vaccines have never been said to be 100% effective on an individual basis.

The definition of vaccine was changed by CDC last year:

https://www.miamiherald.com/news/coronavirus/article25411126...

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.

Original press release: https://investors.modernatx.com/news/news-details/2022/IAVI-...

Is this a measles type of vaccine or a covid type of vaccine?

Since the mRNA covid vaccines seem to only work for 90-180 days, why would a vaccine for anything else be different?

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.

AIDS and COVID are extremely different.

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?

> We could be getting even closer to stopping the spread of HIV/AIDS.

Not if it's anything like the Covid-19 vaccines that don't stop someone from contracting or spreading it.

it's defense in depth.

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.

I love the progress we are making with vaccines.

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.

This is, of course, easier said than done.

https://www.aidsmap.com/about-hiv/search-hiv-prevention-vacc...

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.

> well actually no it’s pretty obvious

If you think they're right you may not understand why the comment is being down voted.

> The current Covid-19 vaccines are proven to lose efficacy over time. Will the same thing happen with this one as well?

Like with any vaccine: Probably.

> It’s a good question

It's pretty besides the point. To recycle my car brakes analogy: They also lose efficacy over time, yet are widely considered to be useful.

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.

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.

Car brake dust is an extremely potent carcinogen, take care when dealing with them.

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.

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.

My God you have it exactly backwards!

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.

> How effective that is for mutated and related viruses is what remains to be seen.

I imagine that depends much more on the virus than on the vaccine.

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.

70% prevention is better than 0%, and something tells me that it will see a much higher rate of adoption than the Covid vaccine.

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.

I think the general public’s perception of the consequences of infection are different depending on the disease.

I think most people see it as “covid = bad cold; HIV = death”.

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.

Car brakes are also ineffective because they don't prevent 100% of collisions, huh?

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.

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.

> 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.

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