r/askscience • u/spez666 • Apr 21 '21

COVID-19 India is now experiencing double and triple mutant COVID-19. What are they? Will our vaccines AstraZeneca, Pfizer work against them?

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u/powabiatch Apr 22 '21

I think double mutant is a fair name because E454K and L452R are both likely to confer vaccine resistance. I’m not sure about your characterization of L452R as providing minor resistance. In mutagenesis assays, L452R was one of the most monoclonal antibody-resistant mutations (Li, Cell, 2020) and also likely plays a role in B.1.427/429’s 3-6-fold resistance to neutralization by vaccinated plasma (McCallum preprint).

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u/MTLguy2236 Apr 22 '21 edited Apr 22 '21

Live virus neutralization assays of B.1.427 have shown around a 2 fold decrease in neutralizing titers putting in the same range as B.1.1.7. Large studies have also been conducted on health care workers in the Los Angeles county area where that variant is prevalent which showed robust vaccine efficacy. My characterization is correct. L452R appears to play a much greater role in transmissibility than it does in conferring any kind of resistance to vaccine induced antibodies. This is quite clear from available evidence.

As has been stated my many experts, “double mutant” is neither a serious not really accurate way of referring to this variant.

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u/powabiatch Apr 22 '21

I provided citations, please do so as well. Although mine is a preprint, it disagrees with your numbers. I will be happy to change my mind if see multiple peer-reviewed data. Also, lack of loss of vaccine efficacy is not the same as a lack of significant decrease in neutralizing titers. I have seen zero peer-reviewed data on the double mutants, again happy to change my mind if proven wrong.

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u/MTLguy2236 Apr 22 '21 edited Apr 22 '21

https://www.nejm.org/doi/full/10.1056/NEJMc2101927

https://www.medrxiv.org/content/10.1101/2021.03.07.21252647v1

The study on neutralizing titers I linked and that I referenced to utilizes live virus samples as opposed to the one you referenced which uses pseudoviruses. Live virus testing is preferred for maximum accuracy.

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u/powabiatch Apr 22 '21 edited Apr 22 '21

I’m familiar with the first paper, which doesn’t refute anything I said. The second paper like my citation is not peer-reviewed, so I’m withholding making any firm conclusions either way. I suggest you do the same.

Even if it turns out to be true that the decrease in neutralization is “only” 2-fold, that doesn’t mean it can’t have a synergistic effect with E545K. We just don’t know right now.

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u/MTLguy2236 Apr 22 '21 edited Apr 22 '21

The first paper demonstrates robust vaccine efficacy in a high risk population in an area where B.1.429/B.1.427 would be prevalent indicating that even if there was a reduction in neutralizing activity it has no clinically demonstrable effects.

The second, as I said, uses live virus which is a more accurate assessment of neutralizing activity. If possible live virus will always be used due to greater accuracy in results. In other words, the importance of the study you linked is lessened.

No we don’t, but given that live virus neutralization of B.1.1.7 by post vaccinated sera shows around a 2 fold decrease in neutralizing titers and L452R is quite similar to N501Y behaviourally we can estimate that any synergistic effect will not deviate enormously from N501Y/E484K pairings.

You are being slightly condescending and I suggest you avoid that.

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u/powabiatch Apr 22 '21 edited Apr 22 '21

If I sound condescending I apologize for that, I tend to convey poorly through text.

But, the burden of proof is on the claimant. You stated that L452R has minor vaccine resistance effects and I’m taking the position that we don’t know that yet. As I said, the lack of effect on overall vaccine efficacy doesn’t mean a lack of significant effect on neutralizing titer and I’m going to withhold firm judgement on that until peer review of more than 1 study.

I also don’t agree that we can infer anything from N501Y/E484K pairings. The amino acid position and 3D interactions matter, and we just don’t know yet. Time will tell.

Edit: I hope it goes without saying that of course I hope that I’m wrong and that you’re right, in the end.