So what? Is it now forbidden to point to possible safety concerns associated with RNA vaccines? Does it make me an anti-vaxxer ? This is crazy! Note that I find @glipsnort attitude toward the point I raised much more constructive, scientific and elegant than yours, for rather than calling to censor me (are you a fan of cancel culture ?), he enters the discussion and makes me see, through a good argument, that my concern was probably not warranted. This is the way forward, not yours, for it is your way that is dangerous, not only for a free society but for science itself.
And that is a good thing, and thank you for stating that. But I think you could have staved off some of the unease by having stated this earlier, in response to @glipsnort, instead of only now in response to concerns about possible anti-vaccine sentiments.
I think we can all do better at acknowledging when we see a good response, myself included. Otherwise we can leave this impression that we don’t really care what is being said on the other side of the argument, and it ends up looking like we’re just taking turns stating things without thinking about the responses we get.
Even small things like “I think I can see what you mean by that, but…” goes a long way.
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Here is the Pfizer vaccine study data which includes adverse event rates.
Anything in particular from the study that alarms you?
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At the moment, the biggest risk to all our health, not to mention our economic and social stability, are people like yourself who are abjectly ignorant of even the most basic scientific information, yet feel justified in making dangerous and ignorant statement like the above.
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If they’re bogus concerns, it’s certainly ill-advised. Your quaint notion that young people shouldn’t get vaccines because they rarely die from covid is more pernicious. And your reference to “cancel culture” makes me wonder if you also think the election was stolen, Obama was born in Kenya, Q will return to save us, etc.
Might I suggest that a better way forward for yourself is to understand your lack of knowledge in the area of vaccines and ask questions instead of giving voice to narratives that could have serious consequences to public health.
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No, you might not, for 1) I have a reasonable good knowledge in the area of vaccines and 2) my concern regarding vaccination of young healthy people stem from the fact that, as expressed in a recent review, « the development of vaccines in a very short time necessarily implies that it is not yet possible to know their long-term efficacy and possible side effects ».
https://www.nature.com/articles/s41418-020-00720-9.
But please note that I am not saying that those who favor the vaccination of young people are wrong, but simply that they might be wrong. IOW, I have no certainties on this issue.
What you don’t seem to understand is the relative risk of the infection compared to the vaccine. A young person will be exposed to the same mRNA during an infection along with mRNA from the rest of the viral genome. On top of that, the infection will expose this young person to much, much more mRNA over a much longer time period. Given the spread of the virus, it is nearly inevitable that everyone will have the mRNA for the spike protein in their cells at some point. The much lower risk exposure is the vaccine. Having immune young people in the population also means they won’t be passing the infection on to people who are vulnerable.
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You have completely misread the article, Gilbert.
The question about the existing vaccines is not whether they are suitable for young, healthy people; the vaccines have been tested and found safe with adults of every age. The only practical issue–and the authors state this quite clearly–is whether the existing vaccines have proved themselves good enough to allow us to stop working hard to improve SARS-CoV vaccines. The authors state that the existing, incomplete knowledge (which you cited) lead not to cautions about using the existing vaccines, but to funding and work on the next generation of vaccines:
The success and approval of the first COVID-19 vaccines should not detract from the enthusiasm and practical possibility of planning new studies leading to the development and production of second and third-generation vaccines [11, 12] as well as the design of different types of clinical trials [65]. Indeed, COVID-19 eradication is going to be a long and winding road that will not finish once we have the first vaccine available.
Normally I try not to be blunt, but when sentiment about a critical set of vaccines is in play I do not hesitate to speak forthrightly. You have lifted one sentence out of the context of the rest of the article, @Giltil, which means you have quote mined.
I do not doubt your sincerity, @Giltil, but I cannot let your (inadvertent) quote mining go unchallenged in a public forum.
Best,
Chris Falter
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Then please use that knowledge to explain your response of citing a second preprint in response to my pointing out that the first paper you cited is irrelevant to vaccine safety–because coronavirus vaccines do not contain the replicase. Art made the same point, but your responses were incoherent.
Are you aware that my point stands even if those chimeras are real?
Besides D614G and N501Y, there is concern over associated mutation E484K which appears to be adaptive and arising in a number of independent lineages.
Due to its rapid spread, the independent origins and the potential implications in vaccination and passive immune therapies, E484K has received particular attention ever since. Importantly, B.1.351, P.1, and P.2 carry this substitution associated with escape from neutralizing antibodies …
The fact that E484K was found in the context of different mutations and lineages is suggestive that this particular substitution may act as a common solution for viral evolution in different genotypes. This hypothesis may be related to the profound impact of the mutation, which changes a negatively charged amino acid (glutamic acid) for a positively charged amino acid (lysine). Since this position is present in a highly flexible loop, it has been proposed that the presence of such mutation could create a strong ionic interaction between lysine (K) in RBD and amino acid 75 of the hACE-2 receptor shifting the major sites of binding in S1 from positions 497-502 to 484.
Preprint - E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil
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It’s that good, old-fashioned evolutionary arms race. Except not so good for us.
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Here in Massachusetts, we’ve had our own lineage with E484K since November, at least. It doesn’t have N501Y and it hasn’t been attracting much attention. One reason is that sequences from that lineage have another deletion that makes the automated software in public databases reject them as defective, so they haven’t been picked up by people scanning for E484K. We’re calling it a database resistant variant.
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Couldn’t this substitution associated with escape from neutralizing antibodies lead to ADE (antibody-dependent enhancement) following vaccination?
Did you not read the article to which you linked?
At this point, I would say that the main worry for any ADE effects would be if the coronavirus mutates to the point that the antibodies generated by the current vaccines become non-neutralizing. And honestly, I don’t see that happening (it certainly doesn’t seem to have happened yet). Targeting the Spike protein is another big benefit that we got from the earlier SARS work; which suggested that (for example) targeting the Nucleocapsid (N) protein was riskier. With the Spike, you put the virus in an evolutionary tight spot: evading the antibodies while trying not to lose the ability to bind to the human ACE2 protein. So far, that looks like too narrow a path for the virus to stumble through.
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Yes. And it is precisely the passage you point to that is worrying in the context of the emergence of the E484K variant, for it seems that this mutation is associated with escape from neutralizing antibodies, hence possibility prone to cause ADE according to the very words of Derek Lowe in his commentary.
Escape? No, it doesn’t seem that way at all if you understand math, immunology, and virology. A log (10-fold) reduction in Ab titer is not that big.
His words say that there is a possibility (obviously) that is not likely; he explains why it is unlikely, which you don’t appear to understand. What do you propose to do? The actual virus is far worse.
What about your claim that the chimeric transcripts are relevant to vaccines? You still haven’t explained that one yet.
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On its face, I’m not sure if I agree with you. If you need 10 fold higher antibody concentrations in order to stop plaque formation in tissue culture that would seem to be problematic. Am I missing something here?
Why?
Lowe explains it very well:
https://blogs.sciencemag.org/pipeline/archives/2021/01/27/vaccination-against-the-new-variants-real-world-data
…it’s important to pay attention to the Y axis on these – it’s a log scale. The bottom of the graph is not a flat-zero no activity line; the bottom is still a hundredfold dilution of the serum from the patients. You have to do that in order to get an assay window to see the differences – straight serum from vaccinated patients should still hammer these viral strains right down. As Burioni says, “ There is a decrease, but from extremely high levels. I think these data are very good “. And I agree. It would be very interesting indeed to see this experiment run with plasma from people who have only had the first shot of each of these vaccines, though, wouldn’t it?
The thing we have to watch for, then, are much larger decreases than the sixfold, 11-fold, 30-fold levels. The preprint from the South African team mentioned above is worth considering in that light. It’s a small sample (six patients) of plasma from people who recovered from “first wave” coronavirus, looking at how such antibodies deal with B.1.351 types. Of the six, the activities are 5.7-fold lower, 9.6-fold, 38.1-fold, 53.2-fold, 204-fold, and one that was a complete knockout. Those last two are of concern, for sure, especially the KO. Now, you’d want to see a larger patient sample, to know how common those big drops are. And you’d especially want to see this experiment run versus vaccinated patient plasma, as shown above, which should be better across the board.
Again, the vaccinations are generating higher titers than infections across the board, so Gil’s attempt to use E484K as an argument against vaccination is utterly specious misinformation.
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Yes, he said in December that the possibility was not likely. However, some few weeks later, it seems that this unlikely possibility has arisen.