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.
> It is not entirely understood why some patients are able to achieve undetectable viral loads without ART.
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?
> 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...
it's really interesting to me that their health becomes poorer earlier, but that it doesn't affect mortality.
And as it's 'just' prevention, it's hard to know whether it will reliably improve this individual outcome...
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://www.virology.ws/2011/01/21/are-all-virus-particles-i...
https://royalsocietypublishing.org/doi/10.1098/rspb.2009.006...
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/
You don’t need to be a 100% sure. Once the risk becomes small enough you can spend your time worrying about other risks.
Hell, an HIV viron could be created spontaneously through quantum tunneling in your body with some non-zero probability. I think it would be legitimate to triple equal signs that to "not going to happen" though.
Time spent driving is not time spent having sex (well, hopefully).
So if risk(dying while driving) ~ risk(dying because of sex) ~ 0, you can easily ignore both of those.
Also, you can avoid having sex with a HIV-positive person. You can probably not avoid driving. So the fact that a risk may be low is not sufficient to take such risk if you can hedge against it.
Meanwhile doing some once a day with a 1 in 1,000,000,000 chance of possibility killing you in 40 years just isn’t worth considering.
Depends what your quality lifespan is. If I get sick of everything, that time isn't worth much.
There's also a "time-value" of life.
Cool stuff I can do today may be worth a lot more to me than things I can do 500B years from now. Especially since the person that would be doing them is someone I cannot identify with at all.
Yes, and I believe this is a reason why people make choices that adversely affect their 50 year old self. Who's that guy in the future going to be? Why should I care about making it better for him?
I can imagine time scales on a par with how long I've lived and to a lesser extent to the ages of people I identify with.
(500 year from now me would see the first paragraph as exceptionally foolish... and also inevitable. But that fact doesn't change the truth of what I'm saying).
The vast majority of virions seems to be killed by the immune system before they can actually take hold.
https://journals.plos.org/plospathogens/article?id=10.1371/j...
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.
Gay people were so stigmatized at the time that the government did nothing when they thought it was a 'gay disease'; they just let an epidemic spread and people die. Very few in the 1980s worried about offending gay people. Once it was spreading to people who weren't gay, then I'm sure health information was provided to those people.
But I just have to laugh out loud at the thought of governments in the 80s not stigmatizing the disease and specifically queer people having anal sex.
Just so laughably the opposite of the real experience of an entire lost generation of gay men.
There's no excuse for it in todays day and age, but what can you do? I sometimes think democracy is a soap opera for serious people, whilst the military run the real show.
There was a thing not long ago where talcum powder, I think Johnson & Johnson, had some asbestos contamination (asbestos being another mineral that can come from the same mines, apparently). And people were suing because it gave them cancer of the uterus and other internal parts of the female reproductive system. Which makes you go: Wait a second. How the hell does that happen?
That's how.
When I first heard about asbestos in children talc powder, I simply thought it was just one of these "bad pharma" conspiracy theories (there was another one - about asbestos in sanitary towels). It seemed so far-fetched - who in their right mind wouldn't make sure to thoroughly check a product designed to have long-term contact with babies' skin against well-known carcinogenic substance? Well, it turns out this time it happened not in China but right in the heart of the USA.
You might find this interesting, the "few years back" might be now again: https://www.nature.com/articles/s41586-021-03901-9
I think this Hollywood film Dont Look Up will be a poignant message to everyone.
I would not use Wikipedia for health information with serious consequences.
I mean, technically, there's always a possibility of getting HIV. Particles in your body could spontaneously quantum tunnel at the same time into the form of an HIV virus. This is basically impossible, but not actually (p = 0.00) impossible.
At some point you have to look at a probability and say - that's basically not transmissible.
You generally can't measure infectious dose directly without a highly unethical challenge study. You can sometimes know concentrations that did or didn't result in infection in various real world scenarios, and sometimes you have circumstantial evidence (e.g. you can know how much virus a person sheds, and what proportion of a room with certain ventilation quantities got infected).
Infection requires virus particles to be physically present in transmission vectors (fluids, droplets, etc). There's generally also a dose-response effect where more particles means more chance of evading the immune system well enough to establish replication in the victim.
So a lack of anything to detect, means a lack of anything to spread an infection.
One should add that for that the threshold for detection has to be lower than the threshold for infection.
Example: let the detection threshold be 10 particles/ml and the infection threshold be 100 particles/ml (*) -> then undetectable implies that it is very improbable that an infection will take place.
(*) This is a very crude description. Think of it like this: Every single virion (virus particle) has a very low probability of causing an infection itself but there is a high number of them and for one them it might just work out (higher viral load -> higher risk of successful infection)
This statement is logical and makes perfect sense - but it's narrower than the original one.
We're quite good at detecting viruses if we really want to. PCR can amplify DNA so much that we can detect even 50 viruses per milliliter of blood. A milliliter seems like actually a lot of blood to get into someone else and your innate immune system is capable of finding and neutralizing small amounts of contagions relatively well even if it's never seen it before. I do suspect this is a statistical impossibility though probably you could somehow get incredibly unlucky, for example in your blood momentarily all the free floating viruses end up in the same bit of blood and that somehow gets into someone else, but I think we can all realize that probability is tiny and in practice I don't think there are any examples of transmission with undetectable levels of HIV.
1 cm^3 is indeed pretty big. That’s 1,000 little millimetre cubes, and we can detect as few as 50 virions in that space!
I will point out though that 1 ml is low for semen (more like 2.5 ml or more).
Think of it like chemistry. Sure, two covalently bonded hydrogen atoms at STP could have nuclei 1cm from each other due to random chance. However, the probability of this happening is so low that it is effectively 0.
If one bounds the risk from HIV from an undetectable partner to an unmeasurably small epsilon, dwarfed by other risks by many orders of magnitude--- the edges where the assertion are false don't matter.
Anybody remember hearing something like this?
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).
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.
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.
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.
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.
Ref: https://en.wikipedia.org/wiki/Simian_immunodeficiency_virus
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.
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)
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.
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).
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).
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).
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.
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.
https://www.aidsmap.com/news/jul-2020/demand-prep-highly-eff...
Does this mean that there is a cure, but it only works if taken shortly after exposure (and for a whole month)?
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.
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.
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...
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
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.
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.
Maybe you can't afford the treatment, maybe you have side effects, maybe you don't know you need it...
And in most countries the treatment is funded by the government.
Descovy appears to be better, but I think it's not approved everywhere yet.
https://twitter.com/scrippsresearch/status/13581208549709127...
This explains the background on broadly neutralizing antibodies that the other commenter `mlyle` mentions. Worth the watch.
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.
> 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.
And yes, AlphaFold is a major milestone, but I don’t think we’ve solved protein folding for good.
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?
*when paid annually
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.
It doesn't seem meaningful to define development time without including all the steps required to provided an available vaccine to the public
That's why the codename for the AstraZeneca vaccine is ChAdOx1, it's a Chimp Adenovirus as host for the sequence. Take this mild uninteresting chimpanzee virus, but tweak it to tell human cells to produce your arbitrary sequence instead of itself. The humans become immune to whatever your sequence was (and maybe to Chimp Adenoviruses?).
I'm sure there are reasons this might be better in some cases, and it involved less bleeding edge technology which made it a safer bet in a pandemic, but the mRNA approach seems obviously more general and even perhaps more re-usable.
Which is a major problem with this technique. One of the other vaccines (J&J?) used a relatively harmless human virus and as I recall, some people with previous exposure had no effect from the vaccine.
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."
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.
Most of the time and cost is associated with the trials - not the actual development AFAIK.
What would be more promising is if MRNA proves to be much more likely to pass trials. I think we need a lot more attempts at different viruses to have an idea here.
Certainly - if this HIV vaccine /does/ work - that's a huge win for MRNA.
> If mRNA vaccine was as magical as it was marketed, we wouldn’t be getting 3-4(and soon 5?) doses of the same vaccine with the emergence of new variants. Rather, there would be delta- and omicron-specific vaccine.
This is nonsense. The traditional vaccines don't work any better. They're worse. This is evidence MRNA is better than traditional vaccines.
Didn’t say they were. Rather that mRNA don’t seem to be approved faster for the new variants.
> This is evidence MRNA is better than traditional vaccines.
Haven’t been following the field that closely. I only seen one pre-print(probably Hungary?) where Sputnik was on par. Would love to see data if you’re willing to share.
Edit: I admit I’m a bit confused since I mixed “traditional vaccines” and Sputnik/AZ together. The latter aren’t traditional since adenovirus-based vaccines haven’t been previously deployed, same as mRNA vaccines.
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...
As I understood it, the actual vaccine was developed super quickly and then everybody waited for the results of the study.
Regulatory bodies need to adjust to the new speed of mRNA vaccine production if we want that sort of release schedule.
It took 2 days to develop the vaccine. https://nymag.com/intelligencer/amp/2020/12/moderna-covid-19...
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.
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!
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.
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.
> 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).
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.
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?
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.
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-...
I said "for Delta". If you read the rest of my comment I mentioned the upcoming Omicron vaccine too.
You said, well, exactly what I quoted, which was that variant-specific vaccines for Delta and Omicron were tried, found less effective than the the existing vaccines, and abandoned. That is false.
> I mentioned the upcoming Omicron vaccine too.
No, you said that after abandoning Delta/Omicron variant-specific vaccines, “they” decided to work on mixed Omicron/Alpha boosters. That is also false. Novavax is planning to trial Omicron-specific vaccine. Pfizer is trialing Omicron specific vaccines, both as sole vaccines and as boosters after existing vaccines. Moderna is, I think, working on an Omicron-specific booster-only (after existing vaccines) approach.
> It turned out that the original vaccine is as effective for Delta, so that work was shelved. Omicron, on the other hand, seems to be evading the immunity created by the Alpha vaccine, so they are actually planning to start producing an Omicron specific booster (or more correctly Alpha+Omicron) after FDA approval.
???????????
The thing he said may not have been strictly accurate but your claim about what he said is much less accurate than that.
mRNA tech is a lot newer than "traditional vaccines". I do not expect that the mRNA process is run at the same speed with the same degree of confidence at the same number of facilities. Yet.
- This isn't really the reason why mRNA is attractive here (see my other comment above). (Though, ability to iterate/try many protein combinations quickly in animal models was helpful).
- Almost no drugs or treatments do we really know the long term picture of. Running studies in a way that lets you detect effects far later in life isn't practical.
- When we're talking about treatments to prevent severe disease, bounding the consequences to be very, very likely to be well below the consequences of the virus times the likely infection chance is "good enough".
Vaccine are building an immune response, they're not drugs that try to cope the symptoms (eg. Panadol) and they are the safest drugs out there.
Is so interesting how people eat Panadol and many other drugs like candies (without reading the KNOWN side effects - which are also nasty), while they focus so much on things they know nothing about thinking that has mysterious "long term effects"
I strongly doubt that Acetaminophen would be approved as an OTC drug if proposed today.
> He died at a hospital in Seattle. His wife, Cindy Engstrom, said he had injured one of his feet in October, accidentally took too much Tylenol for pain relief and suffered liver damage.
Once I realise that the Flu (or whatever) is inducing enough pain that I can't ignore it, or I start to run a serious fever, I take paracetamol to get on top of that, usually in the form of Lemsip because I'm bad at taking pills, Lemsip is cheap, and none of the other ingredients in ordinary Lemsip these days really do anything much, just the paracetamol.
I find maybe 1 or at most 2 of the "maximum" 1g (= 1000mg) doses a day gets the job done, which is well inside the indicated limits.
None of the OTC alternatives do it for me, they're not useless but the effect from the indicated dose is far reduced so I'm glad to have paracetamol. I've had fentanyl after surgery, which was certainly effective but seems like a very bad idea to have around the house, and Entonox after a road accident which again, effective but seems like a bad idea for OTC usage.
Popping NSAIDs multiple times a week on a regular basis is definitely not good, and yet the same people who do that are often afraid of vaccines.
People are seriously clueless about relative risks.
I'm not saying Advil is dangerous, I'm saying people significantly overestimate the risks of vaccines.
If you're concerned about vaccines but not about other common drugs, you're in need of some risk calibration.
The good news is that I am not concerned about the safety and efficacy of vaccinations. I misinterpreted your comment because of the way it was worded. This is because I know some over the counter pain medications, like Tylenol, can be dangerous. So, I assumed there was a risk to Advil that I wasn't aware of and wanted to know more, given your background as a Biochemist.
Also, NSAIDs are shown to slow healing from injury in most cases.
Ibuprofen is terrifically useful but also a little scary for something we use so routinely.
e.g. some parents gave their 7 year old a motrin, and all her skin sloughed off her body and she had brain damage and lost 80% of her lung function.
https://www.cbsnews.com/news/jury-awards-63m-to-samantha-rec....
And fatal anaphylactic reactions to vaccines aren’t atypical.
My point is not that Advil is particularly dangerous, my point is that people dramatically overestimate the dangers of vaccines.
Look at Vioxx. It took 4 years on the market before anyone realized it increased the risk of heart attacks.
Advil has been around for decades. It has known risks.
I have all three vaccine doses too, I’m not saying don’t take the vaccine, I’m saying Advil has a more robust safety profile.
Other drugs don't have a better safety profile if they were tested for so long. If anything, it proves that is highly toxic for your body (similarly to many chemio treatments)
Covid has been around for 2 years. The vaccines for 1 year. We don’t know the long term effects of either.
Vaccines were trialed for dengue fever that made the disease worse. Vaccines are NOT “the safest drugs out there”.
Anyone who says “the vaccines are the safest drugs out there” is just lying or incompetent.
The risk of an autoimmune disorder may not show up for years.
Our data collection right now is garbage and it’ll take years to sort through.
"Autoimmune disorder" probably have a very low correlation and if anything vaccine have saved the life of many, more than any other drug.
This is because there generally isn't a known mechanism for vaccines to have long term effects. Not ruling out the possibility, but we understand how vaccines work pretty well. Also, most vaccines are subject to a cost/benefit analysis anyway (we don't give the rabies vaccine out to everyone) so the miniscule chance of having long term effects has to be weighed against the much more likely long term effects of the disease.
I know a lot of people believe this, but as a developer who regularly deploys code to production, this mindset blows me away.
I'm not saying that being a developer means I know anything about this. I'm well aware of my (our? I don't know what you do) peoples habit of thinking being good at our craft means we're also somehow suddenly good at others.
But if I told someone that I don't need to know the effects of v7.1.3 before patching it because I can't think of a mechanism for it going wrong, and besides, we already released all those other versions and they were fine, I'd hopefully be fired.
I get it, software and medicine are different things, and some things just aren't practical in meat space, but the mindset around testing is something that I think will always be difficult for me to understand after being in this occupation for so long.
You are missing the point. If someone told you they are worried that your code is going to turn the CPU into strawberry jelly, you would be correct if you said 'there's no known mechanism that will cause that'.
It's not quite strawberry jelly, but depending on the target you're writing for, you could destroy the actual hardware (think embedded devices).
If you presuppose that adverse effects can't happen, then sure, your quip makes sense. But pharmaceuticals having adverse effects isn't some unimaginable thing, it's expected and tested for.
Not for potential issues tens of years later, which is basically the concern people are raising about these vaccines. We instead look at known potential mechanisms that could cause harm and operate off of that.
We have studied the short term side effects of these vaccines, much we do anything else, and have looked at known potential mechanisms that could cause issues down the line, and have not identified any. This is more or less the same standard applied to just about any medical research for drugs, vaccines, other treatments, etc.
I am concerned about tens of years later, but also about just ones of years later as well. We've done the best we can so far, and it seems like a clear win for some categories of people. For others, it's not so clear (like young healthy people with a previous infection living in the age of omicron for example. This is not medical advice, go to your doctor for that).
> This is more or less the same standard applied to just about any medical research for drugs, vaccines, other treatments, etc.
Sure, but I'm not chomping at the bit to take any more of those either (already had all the usual vaccines and then some, minus flu). And those other things have been around long enough that adverse effects eventually become unmissable. You see those occasionally in class action commercials.
That reminds me of the first atomic bomb test. We weren't 100% sure that the atmosphere wasn't going to ignite with an atomic bomb, but those that knew the physics knew it was almost impossible.
> "If, after calculation, [Compton] said, it were proved that the chances were more than approximately three in one million that the earth would be vaporized by the atomic explosion, he would not proceed with the project. Calculation proved the figures slightly less -- and the project continued."
https://www.insidescience.org/manhattan-project-legacy/atmos...
Of course it can, that's what you use to write your test plan. But I never (ever) rely on those predictions alone. Everyone who has done this long enough knows that if you don't test your code well enough before you push it out, it will fail. Hell, it'll even fail sometimes when you did thoroughly test it.
If you had to push code and wait a year for feedback then how you tested and pushed code would change dramatically.
Now imagine the environment you were pushing code to was
1. Always changing in very small ways that could sometimes have huge affects due to completely random variable changes you had no control over. 2. Every host your ran your software on 'could be' different in ways that are incompatible and you have no way of testing all of them.
Welcome to the problem space of biology.
But this isn't what they're saying. They're saying that there are few to no ways for it to not have any detectable issues for 6 months and then suddenly go wrong (which I'll note is also true for software!). Canarying and staged rollouts are a good idea in software, as they are in medicine. But much like you don't think its necessary to canary v7.1.3 for a year, just in case it has a bug that makes it shut down suddenly after 200 days, its probably not necessary to wait a year to see if a vaccine causes sudden acute liver failure after 7 months, because there just isn't a biological mechanism for it to do that (the vaccine is already out of your body by that point!).
And to the extend that such issues are possible (leap days can do weird stuff), we can look specifically for those mechanisms (like say monitoring for stuff that would lead to liver damage in the weeks after vaccination).
Over the years I've become a little obsessed with imagining the ways things can fail (I'm just as fun at parties as you can probably imagine).
An example that immediately jumps to mind where that is not true for software would be something that quietly uses some resource that you didn't expect (open ports, filehandles, space on disk/memory, the space inside of however many bits you have for a field, anything like that). These are things that you don't know to test until you've seen them fail, and only then can you start to automate.
One possible analogy here is cancer or autoimmune issues. If you get diagnosed with either of those today, they almost certainly started a while ago, they just weren't detectable until today. Or maybe they would have been if you knew exactly where to look, just like if you knew to keep an eye on how many ports you had left on your live server. (Not claiming these vaccines cause these things, I'm sure some peoples blood pressure started rising as they read this).
The complexity of software is nowhere near that of the human body or populations of humans, and yet it can be incredibly hard to predict. Multiple backwards compatible versions on the client and server side, running on different hardware with different operating systems, all of these things changing over time. Unexpected behaviors can absolutely show up at any time.
Of course you can't test it all, but you do what you can, and then after that you monitor very carefully, but its way more expensive to fix the problem after it reaches prod. In humans, there's a chance that its not just expensive, it's impossible.
Some engineer creates a fix by turning off some recently added experiment responsible for the service degradation. The rollback passes all unit tests and integration tests. You know this fix is low-risk (maybe because your service was healthy for the ~1 year prior to the rollout). Even if there is some risk that this rollback breaks the service at some point in the future, in comparison to the known revenue loss the expected loss of that breakage would be minimal.
Another engineer objects to the rollback saying that "they don't know of the long term effects of such a rollback." You try to counter their claims by showing that previous rollbacks were almost always successful, and when they caused another failure that failure was not nearly as bad as the original service degradation. Also, the rollback passes all tests. That engineer then repeats "we don't know of the long term effects of this particular rollback, and I'm skeptical that the fix is good because the failing experiment and rollback was identified so quickly."
(Rollback vs. fix-forward doesn't actually matter; the point is that all available knowledge shows that the fix is low risk, historically supported, and that there is likely no mechanism for random failure in 6+ months.)
Do you think it would be correct to prefer the second engineer's claims?
But the assumptions that you use to calculate that net are where all of the disagreements stem from. In your example, you've constrained it to losing well defined revenue, and "you know this fix is low risk", so the answer is easy.
Maybe (wrongly or rightly) you don't have faith in the revenue numbers, or in the test suite or the engineers writing the tests or the fix, maybe there's office politics involved, etc.
This thread started with my reaction to these lines from op:
> Knowing long-term effects (1+ years) is not a precondition of approval for most vaccines. It just so happens that vaccines usually take a long time for approval, so we end up knowing long-term effects as a side effect. This is because there generally isn't a known mechanism for vaccines to have long term effects. Not ruling out the possibility, but we understand how vaccines work pretty well. [...]
I've seen this claim dozens of times, and it always always always makes me think of those scenarios where you find a bug in code that you or someone you trust/respect wrote from the ground up, and you wonder "how in the f*** did this ever work?". I'm not claiming I'm right to feel that way, maybe this is a defect in my character, but I just can't buy the "we understand vaccines pretty well" thing.
You seem to be taking this from the perspective that, because there are unknowns, literally anything could happen. And we don't think that's the case with my vaccines or code.
Pushing v2 of your webapp to master isn't going to cause rockets to launch. There are things that could happen and there are even very surprising things that are unlikely but could happen. But not everything is possible.
When we say "we understand how vaccines work pretty well", we mean that in the same was as "we know how our app works pretty well". That doesn't mean that we can't still be surprised, but it does mean that we have some things that we can be confident won't happen.
One such thing is sudden onset symptoms well after the thing has left your system, because there isn't a biological way for that to have an effect (to use the code analogy, you enable an experiment, it modifies database writes for a while, then you disable the experiment and delete the code. Once you've deleted the code, we know it can't do anything else, because it's not there anymore.
That's true with both vaccines and webapps.
The hard part about conversations like this are that you could have written the definitive book on this stuff, or you could be just another dummy on the internet like me. So I have to take a statement like that and do my best to evaluate it myself, since I have no idea how to value your expertise. If you're an expert of some sort, I apologize in advance.
We know for a fact that vaccines have long term effects. They wouldn't be useful otherwise. It would be nice if they could only have positive long term effects, but why would there be any guarantee of that?
Symptoms could start immediately but be undetectable until they progress far enough (think a tiny little tumor for just one example). Again, not claiming this is happening, just saying that it seems nutty to assume it can't happen.
When I read "we understand how vaccines work pretty well", I automatically translate it to "we understand pretty well what happens when we inject a substance into a human body", and then I think "really?". We have some useful models, sure, but "understanding pretty well" seems a vast overstatement of the situation, especially when its laypeople chatting on the internet.
The abstract concept of a vaccine is pretty simple. Anybody can regurgitate the picture book version of it. Any specific instantiation of one is remarkably complex, all the way from manufacturing, to transport, to administration, and then interacting with the legacy ball of spaghetti that is the human body and it's various systems.
The fact that we humans decided to name some substance the same thing that we named some other substances that we created in the past doesn't necessarily tell you how that substance is going to interact with the body. It can provide you with hypotheses, but hypotheses need to be tested.
Correct, but, and this is the important bit: the only lasting thing the vaccines do is leave your body primed to react to certain proteins (everything else they "do" leaves the body pretty quickly, you can think of this as a fairly limited api they're interacting with). This could be a bad thing, but if it is
1. Anyone who naturally caught covid would also suffer the same consequences
2. you'd expect to see the issues as soon as the immune system was primed, this takes days to weeks, not months.
So yes, there are all sorts of weird thins that could happen, but I'll reiterate: we know of know biological mechanisms that would make those things happen suddenly, without warning, months after the vaccine. We understand, very well, that such things can't really happen.
Just because you don't understand the human body very well doesn't mean the medical establishment also has equally no clue.
That is of course the goal, and assumes nothing goes wrong in the manufacturing, transport, or delivery mechanism for the payload. But if they haven't been tested for long term adverse effects, how do we know this? And again the answer ends up being because we know how vaccines work and round and round we go.
But let's leave that and assume that it actually does verifiably only prime the immune system to react to certain proteins. Is that some small thing? Immune disorders can range from annoying to horrific, and they're all from just reacting to certain proteins.
> This could be a bad thing, but if it is 1. Anyone who naturally caught covid would also suffer the same consequences
This seems to be a hypothesis. The current vaccines are based on a modified little chunk of a now extinct(?) variant of the virus plus some novel packaging. That they should have the same effect on the body as the whole current or future dominant variant (edit: entering the body via a different pathway) doesn't seem obviously true.
> you'd expect to see the issues as soon as the immune system was primed, this takes days to weeks, not months
Why? I'll use the same example again. If a tiny little tumor were formed, or would be formed over time as a result of some protein reaction that started right after being dosed, why would you expect it to be detectable immediately?
The specific mechanism isn't important, it's just the "we can't think of a way it could fail, therefore we dont need to verify this" is just impossible for me to get my head around.
Feel free to drop the conversation if this gets frustrating. I will continue to ask until I understand, and I may not get there. I'm actually enjoying this, but I know I'm weird and this drives some people nuts.
> Just because you don't understand the human body very well doesn't mean the medical establishment also has equally no clue.
Fair, but that's not my claim. I can be at 1, while the medical establishment is at 100, and actual understanding of what's going on in the body could be 10000. We do some black box testing and get some somewhat repeatable results. That's a pretty amazing feat, but still a far cry from really understanding what's going on under the hood.
Pushing webapp code to master certainly won't result in rockets launch, if only because no sane person physically connects launching platform to build server ("no biological pathway"). On the other hand, deploying build artifacts carries much more risk. This risk is usually mitigated by extensive multi-level testing and appropriate live monitoring. In addition, the target environment for software is, at least theoretically, fully tractable. I.e. it can be de-constructed and understood to the very last bit. It is also fully human-made and controllable, without random nuclear reactors hooked up to web server. If such invariants cannot be established, I think it is not ethical for a senior software engineer to approve mandatory wide-scale deployment. Under such conditions the decision must be strictly on the owner of each server.
In case of vaccine we deal with infinite number of reasonably unique "environments" - human bodies. We know that each of these "environments" are absolutely capable of developing a million of adverse things like cancers, strokes, autoimmune diseases, etc. So, the "biological pathway" exist, the "rocket launchers" are there. Our understanding of inner workings of human body is very imperfect, as demonstrated by the fact that humans still suffer and die from all sorts of diseases. Our monitoring tools are very limited, and our analytical framework is just blunt statistics. The vaccine is, basically, a clever hack into a half-understood system. So, it is certainly up to the owner of the body to decide what to "deploy" into it. And disagreement or misunderstanding, in my opinion, is exactly around the concept "who really owns one's body".
The database analogy is also interesting, in that while the experimental writing code is gone, the database remains modified. In sufficiently complex and poorly understood system how can one guarantee that modified data doesn't cause any unhandled exceptions down the track, especially given the number of vulnerable third-party clients?
I'm not against vaccines at all for the record. But this doesn't seem like a strong argument for them.
Cells multiply by themselves all the time. Triggering that effect is how you get cancer. Your heart beats constantly. Triggering that too much (or in the wrong rhythm) is not a good thing. There are probably a ton more examples.
Those are wrong analogies though. Vaccines don't trigger something too much. They trigger the exact same mechanism that will be triggered anyway when you get infected with the actual virus, but in a safe way.
However, with HIV as with COVID, there's a pretty significant installed base around the country so showing that it works isn't really a challenge.
Usually only a few thousand or tens of thousands of folks participate in basically any drug trial, btw. We very well understand the risk profile of mRNA vaccines at this point, having deployed billions of them and studied the technology for 40+ years. And having studied vaccines for upwards of 300 years.
What you define as "long term"? Because in my definition, in the "long term" we're all dead.
The "long term" effects of many pathologies is also death for example.
My wife's studio got a "everyone who takes the vaccine will die!" pamphlet pushed under the door, which gave us a good chuckle.
I ask that you please speak to some people in South Africa or Botswana where almost 20% of the population live with HIV, including children (both victims of rape - there was and still is the belief that having sex with a virgin can cure AIDS - and children of HIV-positive mothers who were born with the condition).
It's beyond inhuman, and if such a vaccine were to work it would be as impactful as the eradication of Polio (yes, I know it still exists in some places) or Smallpox.
So more likely you’ll just get over a shorter release cycle and the longer one gets deprecated, relegated to certain style of treatment that mRNA based investment and research will run laps around anyway, further pushing people to evaluate and prioritize mRNA versions.
You can try to hold out for an arbitrary threshold of “long term” for your own comfort level. Its accurate that the state wont be helping you.
mRNA is like a file for a 3D printer, telling the body what to print for. Other styles of treatments were showing the body the payload. We will definitely learn how often we can get the body to do this, but I wouldn't call it an inferior beta status. Its just as good (or bad) as the longer process for different kinds of treatment. Same efficacy, which allows me personally to not focus on that.
What a bizzarely banal thing to post.
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.
Because sex is good. And sometimes spontaneous. And often combined with other drugs (booze) and people make bad decisions.
Is it gonna be “one or two shots one time” like the Covid vaccine was initially pitched or ...
- Flu. Twice per year until age 9 then one per year, forever.
- Td, one dose every 10 years, forever.
- Tdap, 4 doses.
- Pneumococcal, 2 doses.
- Rotavirus, 2 or 3 doses.
- Meningitis, 2 doses.
- MMR, 2 doses.
- Hepatitis A, 2 doses.
- Hepatitis B, 3 doses.
- HPV, 2 or 3 doses.
- Polio, 2 doses.
- Varicella, 2 doses.
Seriously, we've had vaccines for 300 years. This kind of shocked Pikachu reaction to the very concept of a booster is tiring and adds nothing to the conversation.
Honestly, one dose every 3 months to avoid AIDS? In a heartbeat. How is getting an ouchie once in a while anything other than a remarkable scientific breakthrough in the prevention of one of the most insidious diseases we have?
That's not at all true, though the number drops pretty low when you eliminate the various series for infants that have doses at something like 2, 4, and 6 months (and often a fourth at 12-15).
But even eliminating those, there's a 3-dose/6-month HPV vaccine series, and a 3-dose, 6-month series for Meningitis B for populations at elevated risk, and maybe others.
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.
Cool! When am I getting my free 5G?
My experience is that as soon as we make a judgement call about someone, and put them in a pre-conceived box that we do agree with, we are unable to learn.
I went and re-read OP post. nothing in it is close to what you are insinuating.
Yes there may be some unsubstantiated claims, or calling out faucci but shutting down discussions with comments like yours are unhelpful.
Considering the rest of the comment and the throwaway account, yeah, for sure the comment was in conspiracy-land.
My comment was useless, yes. Flagging it was probably much more impactful.
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.
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?
Can someone with more knowledge explain the thought process behind this?