A year or so ago, the news was filled with daily announcements that a miracle vaccine was being developed for covid.
Every news agency proudly reported on its local favorite son-(usually the local university or department of health, or an expert located far away but who had begun his career at “our” university) They proudly declared that help is on the way, and we are the ones who will save you. British sources reported on AstroZenic and Oxford university. American sources spoke of Pfizer and . a half dozen other companies, all of which were just on the verge of great discoveries.
Then the vaccine actually became available, and, by george, it actually worked. So things were looking good…until the Delta variant showed up.
And for the past several months,—silence.
I haven’t seen any news stories about research into a vaccine for Delta.
Not only is nobody making grandiose predictions…nobody is offering any info on whether researchers are even trying to find a vaccine to beat Delta.
What’s up? Why the silence? Or is it just me, and I should be embarrassed for not noticing?
(note to mods: Although this is obviously about covid, I put this in GQ and not the Quarantine forum, because I see it as a question about news reporting and science… The Quarantine Forum seems to be mostly about people’s experiences with the disease.
Yeah, the vaccines that went public starting last December were really insanely effective. Now, versus Delta, they’re slightly less effective, but they started off so good that “slightly less” is still extremely good.
And it isn’t clear that the increased contagiousness is actually due to significant structural changes in the spike protein versus just replicating faster and more prolifically, so when people started easing up on masking and restrictions on indoor activities, the higher viral loads just resulted in more infections even among people who were vaccinated.
It should be noted that the way vaccine efficacies were sold to the public based on trials led to them being somewhat oversold; both the Pfizer/BioNTech and Moderna vaccines relied on self-reporting of participants who were symptomatic; thus, the 90% and 95% efficacy was derived from symptomatic vaccinated from symptomatic unvaccinated. In reality, we know that at least 50% of people with the original “wild type” virus that the vaccines were tested against were non-symptomatic even in the unvaccinated population, so assuming the vaccine helps the immune system suppress symptoms and people were generally taking more precautions resulting in lower viral loads in infection, a substantial number of vaccinated people may have still been infected but not felt or reported any signs or symptoms. Parts of the Oxford/AstraZeneca trials did do systematic testing which may explain the lower (and perhaps more realistic) efficacy numbers.
Regardless, the vaccines are still remarkably effective in preventing severe morbidity and mortality to the point that only a tiny fraction of hospitalized people are fully vaccinated, and of those who are the vast majority had pre-existing severe co-morbidities. Vaccines are also believed to be effective in reducing both the period and amount of viral shedding based on epidemiological differences between vaccinated and unvaccinated populations (although it is very difficult to establish this exactly without culturing actively shed virus in plaque assays).
I know that Pfizer did look at a modified vaccine specifically for the ‘Delta’ and other various of concern, and concluded that the current vaccine suitably boosted would still be expected to provide robust immune response against severe morbidity and mortality, hence why both Pfizer and Moderna are campaigning for comprehensive ‘booster’ doses; the reality may be that in the exigency of getting wide deployment of the vaccine that it was not realized that this is a three or four dose vaccine, and that the supposed ‘boosters’ should actually be part of the standard vaccination schedule. Normally after the standard three phase safety and efficacy trials (that, just to be clear, all of the vaccines went through to the normal statistical standard of safety and function) the third phase study is extended over a period of a couple of years to assess longevity and the need to adjust dosages or for additional shots. In this case, we are running that long term study in real time, and from what are now multiple data sets, immunity does appear to be waning, suggesting that additional shots are probably necessary to get robust, long term immunity.
To add to what the others have said, what would be the point? The current vaccines are still EXTREMELY effective against hospitalization and death even against the Delta variant. They’re just not as good at keeping you from getting sick at all.
Which is pretty remarkable… your normal flu vaccines are something like 65% effective at keeping you from getting sick. The COVID vaccines are that low only after six months.
I suspect that when things calm down again, we’ll actually see mRNA flu vaccines pretty quickly in the grand scheme of things. And they’ll be more effective and hopefully more targeted, since once they’re developed, they can be tweaked very quickly (it took the BioNTech team like a weekend to tweak their SARS vaccine to be effective against COVID), so they might be able to either delay vaccine production a bit later until the prevalent strains are identified, or maybe tweak it midstream.
and why does anyone even think that SARS2, covid19 , will ever need a new vaccine ?
The spike protein targets the human ACE2 receptor.
These things are like the keys and lock … the lock is the ACE2 receptor, and it remains the same, its even the same in all humans. … so the key, the spike protein must remain pretty much the same to attack the ACE2 receptor. It would be a big jump to attack a different receptor, and how could it evolve that ? the mutant version of the virus which is half way to attacking a different receptor would be halfway away from attacking ACE2… it wouldnt be a viable mutant. Now of course its possible that it could jump host species and find a path of stepping stone receptors toward some other human receptor…but in that case its possible to detect it in the animals… which is why big countries have animal virus research labs ( eg there was a case of Hendra , in a horse, near here. so far its not transmissable from human to human … but well if it can kill one human, why shouldnt it be able to be contagious between humans ? maybe it will mutate ?)
Then even if the spike protein of the sars2 virus changed a bit, well the way antibodies are designed by your body, it starts off with a design and randomly changes it until it works better… and then uses that one. So being vaccinated with the original covid19 spike protein is going to be a good headstart for a slightly modified spike protein … there’s little change required to adapt it to work.
The reason they wanted to try an inhaled vaccine was to see if they could make a vaccine that very likely prevents any symptoms at all, by training your immune system to protect your membranes.
This is like Salk vs Sabin for polio … Salk is injection, so you can still get polio infection in the membranes of your GI. But you are protected from the permanent illlnesses that result when it gets into your blood… your system in general… Sabin is Oral… this trains the body to fight it in the membranes, so that you can’t even get it , you are far less likely to be contagious, (but sabin is attenuated live vaccine, so you can get polio from it as one in a million chance. )
Although the virion needs to be able to interface with the angiotensin converting enzyme-2 (ACE-2) receptor protein, it is not as if there is a one-to-one correspondence that are “like the keys and lock”. The SARS-CoV-2 virion is evolved to be able to interface with the ACE-2 receptor but it is not a perfect or complete replication of the correct ligand, and there are changes in amino acid sequence coding for the spike protein (S-protein) that can make it better or worse at binding; in the case of SARS-CoV-2 “variants of concern” for being more infectious including L452R, E484K, N501Y, and most recently N440K and G446V.
It should be evident by now that the immune response provided by the current vaccines is not perfectly protective (so-called “sterilizing immunity”) even with the original “wild-type” virus and that the variants are somewhat more able to evade immune response and/or are so prolific as to overwhelm response. If it is not apparent, there are many other human-infectious viruses, most notably Influenza A, which undergo antigenic shift sufficient to require vaccines to be updated annually, so this is not a novel capability of SARS-CoV-2.
Yes, there are people who may refuse vaccination because of a pathological fear of injection. It is a recognized condition of blood-injection-injury type phobia in the Diagnostic and Statistical Manual of Mental Disorders (DSM–5 ) and is estimated to affect more than 3% of the population.
Aside from that, injection requires training, equipment equipment, and produces hazardous medical waste (sharps). An inhalant or oral vaccine that doesn’t require freezing and elaborate preparation vastly simplifies distribution, particularly to developing countries that cannot sustain cryogenic chain logistics and do not have a large population of literate people who can be trained in medical procedures.
Influenza is far different, especially as it doesnt use such a simple such as target one lock with one key…
Influenza eg the pig host evolution "hypothesis is supported by the presence of both SAα2,3 and SAα2,6 linkages in pig trachea
I skipped saying that the single spike protein to single receptor thing is limitting its evolution .
Its not true that influenzas abilities say that covid19 is just as easy to mutate as influenza. anyway, influenza isn’t that fast and the vaccines last a few years at least. You did a lot of saying I’m wrong with facts that say Im mostly right.
I have a friend who got J&J because he’s terrified of needles. He’s planning on getting a booster shot, but he’s not looking forward to it at all. Yeah, if he had any other reason to be vaccine hesitant it would certainly push him over the line.
Those aren’t vaccines specific to new strains because the old ones don’t work any more. Those are vaccines that would work against all of the strains, just like the original ones, but do so even better (in various ways).
If they ever make it into production, that is. The original vaccines would be enough to end the pandemic, if we could just get everyone to get them. And the new vaccines will be resisted by the same people who resist the original ones.
Stop thinking in terms of the metaphor of “one lock with one key”. This idea is skewing your understanding of how the virus works. The ability of the SARS-CoV-2 to bind with the ACE-2 receptor is not based upon one unique amino acid sequence, but rather any of a large variation of adequately conformal sequences that map close enough to the angiotensin-converting enzyme (2) to be able to exploit that receptor which is found in a diverse array of cells. It is more like a picture that one can alter your appearance to look more or less like to the point that you can convince someone that it is you.
I did not say that SASRS-CoV-2 can mutate as rapidly as Influenza A; what I said is that many viruses that infect humans can undergo changes via random mutation (as well as genetic swapping in the case of influenza) that allow them to evade acquired immunity and reinfect people, so the ability of SARS-CoV-2 to do so is not novel. In the case of Influenza A, it can undergo both antigenic drift and antigenic shift rapidly enough that, yes, seasonal vaccination is required to provide adequate immune response, hence why annual vaccination to cover the strains and variants that are expected to be most prevalent.
In the case of the SARS-CoV-2 vaccines, they are still quite effective even against the more infectious variants, but many virologists fully expect that variant will emerge with a substantial capacity to evade immunity provided by the current vaccines:
As long as a significant number of the world population is infected with SARS-CoV-2, mutations will continue to occur because of the huge number of genome replications and error-prone replication. Therefore, new variants will continue to emerge, and some of them may pose a greater risk for immune escape. A selective pressure of adaptive immunity was minimal in the primarily naive world population, so most of the variants now present are the result of mutations derived by selection based on fitness advantage. The selective pressure for escape variants will probably increase as herd immunity is approached. In addition, the co-circulation of major variants in the same geographical region, already seen in many parts of the world, may enable recombination, bringing together mutations responsible for different consequences. Thus, the emergence of variants capable of immune evasion seems inevitable, and it will be important to evolve pandemic countermeasures accordingly.
The key point is that to date, the existing vaccines are very effective against all the known variants. And there are certain costs to using a new vaccine. There are apparently biological costs that I read about but don’t understand well, but there are also the routine costs of testing, production, regulation, etc. As long as the existing vaccines continue to work stunningly well (and they do), there’s no hurry to get anything else to market.
More to the point is that we don’t really even have a good way to evaluate the efficacy of a hypothetical “improved” vaccine; The idea that we can run some kind of de novo trials of a new vaccine is undermined by the fact that so much of the population (of the developed world, at least) that has either been vaccinated or experienced prior infection that there is no longer a pool of unexposed people to test a new vaccine against to evaluate comparative effectiveness. We have seen some level of immune escape (although whether this is due to genuine evasiveness of the Alpha and Delta variants or just because they have become more proliferate and exposed people to higher viral loads coincident to the easing of public health measures is unknown) but the that vaccines are still highly effective in terms of severe morbidity and mortality indicates that they are still prompting and effective response sufficient that it would be very difficult to establish the true efficacy of an updated vaccine. (Arguably we don’t properly understand the relative effectiveness of the vaccines we have now because of differing ways in which they were evaluated.)
We should be fully prepared to inform the public of the emergence of a true strain (e.g. a variant that shows significant escape in terms of severe morbidity and mortality) and develop and deploy a new vaccine, but for right now the focus should be distribution of the current vaccines and improving our knowledge of the appropriate vaccine scheduling which probably means so-called ‘booster’ shots as part of a standard three or more shot protocol as well as altering the intervals between them, and getting those distributed to populations worldwide so as to forestall if not completely prevent the emergence of vaccine-escaping strains. If we had the pandemic suppressed to the point of being an endemic illness we would at least have epidemiological space to surveil and evaluate genomic changes instead of trying to catch up months after the emergence of new “variants of concern” because of the overwhelming amount of infection. If we’d had the genomic analysis available at the beginning of the the HIV epidemic that we have now it would have been a completely different ballgame in terms of understanding how the disease spreads and the effectiveness of various measures in containing it instead of the guesswork that epidemiologists had to work with through an entire decade. That we can even track minor genomic alterations in emerging variants is a marvel of technology but the effects are limited by the sheer degree of contagion to try to collect information about.
In short, the focus should be on getting as much of the global population immunized with the highly effective vaccines we have instead of spending a lot of effort trying to wantonly guess at what will come in the future. The more we can curtail spread of the virus, the longer it will take to develop escaping variants.