One reason is because they've found that simply boosting with the original mRNA gives a massive spike in protection even against Delta, apparently on par with variant specific versions of the vaccine.

Another is that recent studies are showing that natural infection provides much more comprehensive, long-lasting immunity against all variants than the vaccination does, while vaccination with the current vaccines offers much more immunity than individuals who have never been vaccinated or infected. So it would seem like the best course of action moving forward may be to vaccinate everyone possible initially to prime their immune systems and reduce the severity of the disease, and then allow Covid to run its course. Eventually vaccinated individuals will have break-through infections, gain the more durable natural immunity, and Covid will become a less serious, endemic virus more like the flu or cold.

In short, we don't yet have a need for a Delta variant vaccine. That may not be true eventually, especially for future variants.

I haven't seen any research that says that infection acquired immunity is stronger or longer lasting than from vaccine. The opposite in fact.

Not an expert, but afaik there's been quite a few studies showing that natural immunity is superior to the vaccine-induced one - I'm also fairly sure that virologists have theorized to that end even before the data became available for the following reason: the vaccine is 100% focussed on detecting the spike protein, so changes to the spike can result in evasive variants. Natural immunity OTOH is developed against more sites of the virus and thus provide a more broad and robust response to variants, present and future.

There's been some mixed signals coming out of the research, but that's in part due to how immunity is being measured. There are definitely some studies showing that particular antibody levels for vaccines can be higher or longer lasting than natural infection, but recent research is showing that those with natural infection have had a far smaller risk of reinfection than those vaccinated, even when controlling for comorbidities. There are still confounding factors, such as behavioral differences between the groups, but its a pretty stark difference. It also makes sense from a theoretical standpoint, as acquired immunity is based on more than the just spike protein, unlike the vaccines, which is a big part of the differences between variants like Delta. The thought is that natural immunity is therefore more resilient to changes between variants.

Its all early enough that its still an open question, but there's definitely early evidence that natural immunity is more resilient than vaccination only.

This was posted last night https://news.ycombinator.com/item?id=28307224

The first thread is commenting on the preprint status of that paper.

Because it means rerunning the trials again.

These requirements will have to be loosened for anti-Covid vaccines. They are tailored to other diseases, but SARS-CoV-2 mutates too fast. The flu vaccine has an exception, too, otherwise it wouldn't be possible to prepare the correct vaccine (against the expected dominant strain) on time.

One bad autoimmune reaction from a poorly engineered vaccine and the whole society will boycott the mRNA vaccines forever after. Safety is higher priority to ongoing viability than speed.

Safety and speed must usually be balanced in a trade-off, and we are actually used to it, that is why people drive a car, even though it comes with a risk of dying or being maimed.

I have no doubt that some kind of safety-related trials must be run on boosters and that they will be run, but they will likely only take weeks in the future, not months.

You presume the time required is a function of something other than observing the physiologic reaction to the inoculation over an adequate period of time.

> but they will likely only take weeks in the future, not months.

We need just one Jesse Gelsinger to shut the whole thing down.

J.G. is a famous case and his death definitely delayed development for a decade or more, but it should be noted that when he died, the technology was extremely untested in humans.

We now have a few hundred million people who got mRNA vaccine and had no trouble. I don't think that even after a death, mRNA would be completely toast. It has already proven its merit.

mRNA?

J.G.'s death involved an experimental modified adenovirus (the same family of viruses used as the vector for several non-mRNA COVID vaccines: Johnson & Johnson/Janssen, Astrazenica/Oxford, and Sputnik V).

The OP was mentioning J.G.'s case as an example of what could happen, too with rushed mRNA vaccines, and that the fallout would be bad.

The number of people dead or severely ill from TTS is already in the hundreds. Where is the boycott of viral vector vaccines?

But it doesn't make sense in this context. They're literally changing nothing except the mRNA sequence.

If a new vaccine is made by taking a gene sequence from a virus protein that's already in the wild, and packaging it into a delivery mechanism (LNP) that's already approved for another vaccine...

If there are any strange reactions to the new spike protein, that would also be caused by the wild virus spike protein, so it's an obvious competing harms situation where the vaccine should be approved, at least so long as the pandemic is ongoing.

Right, all you're changing is the mRNA, but that can still be really dangerous. What if you code for a protein that causes cross-reactivity with a human protein and you give millions of people an auto-immune disorder?

I'm 1000% pro mRNA vaccines and pro covid vaccines, but they still need to be tested.

Then the virus variant itself would cause autoimmune disease, and we'd have a much bigger problem than deciding whether to approve a new vaccine.

For fuck's sake, I'm not saying do no testing. I would assume they do basic checks, first in humanized animals, then using bioassays to try to detect all sorts of problems including antibody cross-reactivity with a wide variety of human cells. I'm also not against a preliminary limited human trial, with bloodwork checked after a few weeks to try to see if the assays missed anything obvious.

Short of that, what do you want them to do? We can't wait years to see if people develop symptomatic auto-immune problems. If we even wait 3-6 months for each new protein, the time advantage offered by mRNA or adenovirus vaccine tech is blown, or at least reduced to the point where there's no ability to react quickly to changing dominant viral strains in a pandemic, or new outbreaks of known diseases.

>Then the virus variant itself would cause autoimmune disease

You clearly have no idea what you are talking about or why the GP comment mentioned an autoimmune disease specifically. mRNA vaccines express specific proteins whereas the virus expresses entire viral molecules. A novel protein expression could cause an autoimmune disease because the novel proteins couls cause the immune system to attack the cells producing the isolated proteins, a problem you wouldnt have with cells producing entire viral bodies.

I think you misunderstood the (G)GP comment which mentioned cross-reactivity, i.e. the immune system's antibodies cross-reacted with both the spike protein and an endogenous human protein, like what can happen with Epstein–Barr virus Nuclear Antigen-1.

The immune system doesn't generate antibodies to an entire virus. It generates antibodies to specific immunogenic proteins or parts of proteins.

If the spike protein resulting from a vaccine causes an immune response that generates antibodies to the spike protein and oops, also some endogenous human protein, that's autoimmune disease.

If you get infected by a virus with the same spike protein, your body will generate antibodies to the same spike protein and also cause autoimmune disease if the antibodies are cross-reactive.

If cells expressing exogenous immunogenic proteins triggered autoimmune disease[1], even the existing wild-type (alpha variant) vaccines would cause autoimmune disease. Presumably that's not happening. The immune system may attack those cells expressing the exogenous vaccine-coded spike proteins, but normal immune systems down-regulate it well enough that it doesn't cause major problems. It would be a sign of a broken immune system if it decided to initiate a long-term attack of human cells just because they once expressed an immunogenic protein. If it did that, any virus would cause autoimmune disease.

Please tell me you work in a field related to immunology and you have a subtler point that I'm missing, and that you didn't just create an account to criticize a point you misunderstood yourself.

[1] to an unacceptable degree. Obviously, things can go wrong with the immune system and almost anything could, if you're unlucky enough, trigger an immune reaction leading to autoimmune disease eventually.

You're making the incorrect assumption that catching some new, dangerous strain of COVID is a guarantee. It isn't.

Pushing out a vaccine that causes harm, even if it's substantially less than the virus it protects against, is asking for a lot of trouble.

Consider two ratios:

Harm ratio = harm caused by vaccine / harm caused by virus

Exposure ratio = projected people who would be infected by the virus / projected people who would take the vaccine

In an airborne, high-R_0 pandemic situation, the exposure ratio is high enough that only one of two cases apply:

1) The potential health problems caused by small-scale exposure to the spike protein alone is relatively small compared to problems caused by infection, in which case vaccinate everyone. This is the current situation.

2) The potential health problems caused by small-scale exposure to the spike protein are significant (for example, hypothetical antibody cross-reactivity with a normal human protein, as mentioned in a parallel comment), in which case obviously don't vaccinate everyone, but lock down the world for a few weeks since having much of the world suffer autoimmune disease is untenable.

The potential health problems are unknown. For example, we are assuming that Myocarditis/Pericarditis is extremely rare, or at least more rare than in a viral infection. Do we really know that, for all age groups and all vaccines? I have doubts, we are still in the discovery phase:

https://www.reuters.com/world/us/us-probing-moderna-vaccine-...

The spike protein is not necessarily a problem, but both NLP and viral vectors have never been rolled at the current scale. TTS seems to be particular to viral vectors, Myocarditis/Pericarditis more so to NLP.

> They're literally changing nothing except the mRNA sequence.

This is like comparing my house to the Willis Tower and saying, "they're literally changing nothing except the blueprints."

mRNA codes for proteins. Coding for a different protein will produce different effects in the body. Most will probably be harmless. If a vaccine codes for a protein too similar to proteins that already exist, that vaccine will produce autoimmune disease.

I think the best solution here would be challenge trials. With it without them we are relying on people getting sick. With challenge trials we just reduce how many people outside the trial get sick as well because we can massively cut down on time. I'd be more than happy to take the new vaccine and get exposed to Delta. It's a easy way to make a huge contribution to society.

Human challenge trials have started in the UK.

https://ukcovidchallenge.com/

Couple of months ago when Pfizer & Moderna were talking about developing variant specific boosters, wasn't the discourse about how the variant boosters wouldn't need full trials again?

isn't the flu vaccine just a cocktail of existing vaccines tailored to the strains we predict will be active?

Sort of.

It's a cocktail of vaccines against the expected dominant strains based on data of strains in the opposite hemisphere because it mutates too quickly to produce a targeted vaccine against any specific strain before it arrives.

But I believe they can develop the vaccine fresh as new strains arrive, as well as reuse previous vaccine strains.

Trials of the Delta vaccine have started https://fortune.com/2021/08/09/covid-vaccines-delta-variant-...

IIRC these trials should last 3 months

I’ve read somewhere that they don’t just take a sequence. There’re some tweaks they make to produce effective immune response. CureVac failed to produce a good vaccine for this reason. My take is that mRNA technology is being overhyped, although it’s a massive step up over other approaches.

CureVac probably failed because they used unmodified RNA base pairs. Both Moderna and BioNTech/Pfizer use modified nucleosides such as N1-methyl-pseudouridine. Extracellular unmodified mRNA - which could arise from the lipid nanoparticles which contain the mRNA breaking down before transfection of cells - can trigger a deleterious innate immune reaction against said mRNA. This interferes with the desired immune recognition of the spike protein. The modified mRNA largely evades that undesired immune reaction. That's probably what sunk CureVac's vaccine.

I think our approval processes haven't kept up with the technology. The existing vaccine is already approved, and boosters seem to have some beneficial affects.

If the GOP weren't so foolish against vaccines, they could have made hay criticizing the slowness of the FDA.

Being foolish against vaccines hasn't stopped conservative media from criticizing the speed of the FDA:

https://twitter.com/RadioFreeTom/status/1429946530782498818

Probably because going through another round of certification is harder than using the existing vaccine as a booster, the hope being that this will already significantly improve delta resistance.

Why not both?

Because pharma companies don’t work for the public, but for the shareholders.

And if they are first to develop a new Delta specific vaccine, they will be making their shareholders money hand over fist

There's nothing to update. The mRNA allegedly encodes for the 'spike' protein, which is the infection vector. The theory at the time was that by targeting that protein specifically, if the virus were to mutate, it would loses it's ability to infect because it could no longer successfully bind to the ACE2 receptors.

In practice, the efficacy is a fraction of what the trials stated it was. It didn't lose efficacy due to the delta variant, the manufacturers just lied about the efficacy by cherry picking the data.

The only option they have now is to blame people's immune systems for lack of response, thus the 'boosters' are needed.

Can you back that up?