Thread by @EllingUlrich

Looking like with the latest turn of direction the virus has managed to escape our immune system efficiently yet again.

There is an unprecedented number of highly diverged variants coming up and two brand-new studies shed light on this concerning situation.

Amazing work!
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In one study, Ben Murrell and colleagues show five-fold escape from serum neutralization by BA.2.75.2 in pseudovirus assay.
biorxiv.org/content/10.110…
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In another very impressive study, Xiaoliang Sunney Xie and colleagues study many current sub-sub variants comprehensively.
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biorxiv.org/content/10.110…

Please read the wonderful threads by the authors themselves for a detailed summary, I will focus on the main take-away.
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https://twitter.com/BenjMurrell/status/1570862185819303937?s=20&t=CUWBvLxsMazKsTSvvycdsA

https://twitter.com/yunlong_cao/status/1570922875590414336?s=20&t=CUWBvLxsMazKsTSvvycdsA

Our immune system works a bit like the guy with a hammer: every problem looks like a nail. This phenomenon is called antigenic sin. Once we have an antibody repertoire, we try to tackle similar viruses with the old repertoire.
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This strategy limits our immune response, but importantly makes it faster and over time can generate and select antibodies that work against a wide range of variants. So there is a reason for it.
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But what we observe now is that SARS-CoV-2 has gone through so many iterative rounds of escape, that we are running out of antibodies neutralizing current variants like BA.2.75.*, BJ.1, BQ.1.1, BA.2.3.20, and many others.
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This was somewhat expected, because we knew that Omicron has accumulated enough change to be poised for complete immune escape.
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biorxiv.org/content/10.110…

The immune escape really appears to be shockingly efficient, new highly mutated variants appear almost every week, and there is no reason to believe that the process will end.
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To achieve this, current variants specifically mutate in the remaining surfaces of the spike protein that were not mutated yet. Therefore, we observe the same mutations again and again: convergent evolution (orange).
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With the cold season starting in the northern hemisphere now incidence has begun to rise e.g. in several European countries. So far this is not primarily driven by the new variants, only mutation of 346 in BA.4/5 plays some role.
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But these new variants will likely dominate in winter. And if they indeed escape the subset of antibodies selected after WT vaccination and Omicron breakthrough, then also our new vaccines are in question, too.
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So what do we do? Start a new primary vaccination round with the highly diverted and convergent variants? One thing appears certain: SARS-CoV-2 is still able to outrace us again and again.
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Thank you for your attention and again: Congratulations and thank you to all researchers and the international research community involved in variant tracking, analysis, discussion, and interpretation.👏🏼👏🏼👏🏼🙏🏼
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