1 of 10: The B.1.1.529 (omicron) Spike looks a whole lot like a 'polymutant' Spike experimentally generated to evade antibody responses from infection or vaccination, as noted by @theodora_nyc.
What does this portend for its immune escape properties?
What does this portend for its immune escape properties?
https://twitter.com/theodora_nyc/status/1464257411582148608
2: @theodora_nyc and colleagues conducted a *super* cool experiment where they drew on their experiments to evolve Spike proteins that were resistant to polyclonal antibody responses, as well as data on escape mutations in natural variants of concern...
nature.com/articles/s4158…
nature.com/articles/s4158…
3: ...to create a polymutant Spike with 20 amino acid mutations from Wuhan/Hu-1.
There was undetectable neutralization of this mutant in the majority of plasma from both infected individuals and mRNA-vaccinated ones.
There was undetectable neutralization of this mutant in the majority of plasma from both infected individuals and mRNA-vaccinated ones.
4: @theodora_nyc points out that omicron's Spike is similarly divergent to this experimental construct and *may* lead to substantial neutralization escape.
But on the bright side, her work shows that people who had been infected then vaccinated retained good neutralization...
But on the bright side, her work shows that people who had been infected then vaccinated retained good neutralization...
5: ...against the polyvalent mutant.
So even if omicron is substantially more 'escapey' than previous variants, excellent neutralization may still be possible.
So even if omicron is substantially more 'escapey' than previous variants, excellent neutralization may still be possible.
6: I speculate that a third dose of mRNA vaccines may afford similar or superior protection against polymutant Spike-bearing viruses as seen in 'infected-then-vaccinated' individuals in @theodora_nyc's experiments.
7: If so, it further underscores the *urgent* need to get serious about vaccine equity worldwide, with so many people still at 0 doses, let alone 3.
8: Lots of speculation in this thread. Caveat emptor.
But the cool thing is that within days we will have data on phenotypic properties like neutralization titers with this newly discovered variant.
But the cool thing is that within days we will have data on phenotypic properties like neutralization titers with this newly discovered variant.
9: The publication of the first SARS-CoV-2 genome by Zhang Yong-Zhen, with the help of @edwardcholmes, @arambaut and @virological_org, led to immediate progress on vaccines and diagnostics.
Similarly, the world-class genomic surveillance in southern Africa...
Similarly, the world-class genomic surveillance in southern Africa...
10: ...and immediate data sharing by @Tuliodna and colleagues, plus the evolutionary foundation built by @theodora_nyc, @jbloom_lab, @AllieGreaney, @tylernstarr etc. (see below), has put us in a position to understand this new variant at breakneck speed.
https://twitter.com/jbloom_lab/status/1464005676842184705
11 of 10: Important to add that T cell immunity and non-neutralization antibody responses are likely to provide considerable protection against severe disease and death even if omicron turns out to be a very serious neutralizing antibody escape variant.
*non-neutralizing
And my apologies to @PaulBieniasz, whose original idea of subjecting SARS-CoV-2 Spikes to the selective pressures of polyclonal Abs in plasma, laid the cornerstone of the evolutionary foundation I discuss above. h/t!
@PaulBieniasz Important: I put a link to @theodora_nyc and @PaulBieniasz's paper in Nature so that you can see that their polymutant Spike work was done with what are called pseudoviruses - harmless virus backbones that express the SARS-CoV-2 Spike, *not* SARS-CoV-2 itself.
Should say 'polymutant' not 'polyvalent' above😖
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