Can someone with more knowledge explain the thought process behind this?
Can someone with more knowledge explain the thought process behind this?
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.
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.
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?