JF on Twitter: "Is there a reason the mRNA vaccines have been tested and approved faster? It makes sense they'd be able to adapt to the spike, since that's what the actual mRNA of the vaccine encodes, but it seems like the regulatory turnaround has been quicker as well, at least in the US.… https://t.co/054RnrKn1d"

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Trevor Bedford‏Verified account @trvrb Feb 3

And importantly the spike S1 subunit is 671 amino acids to HA1's 328 amino acids and so we might expect a ~2X rate difference just based on protein length as target for mutations. 9/18

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Trevor Bedford‏Verified account @trvrb Feb 3

For the fastest evolving seasonal influenza virus A/H3N2 we see a steady accumulation of ~2.5 amino acid substitutions per year over the past 12 years, which is slightly slower than what we're seeing now in SARS-CoV-2. 10/18pic.twitter.com/AfazhzCqkI

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Trevor Bedford‏Verified account @trvrb Feb 3

Other seasonal influenza viruses evolve more slowly with A/H1N1pdm showing ~1.5 substitutions per year in HA1, B/Vic showing ~0.5 substitutions per year in HA1 and B/Yam showing ~0.7 substitutions per year in HA1. 11/18pic.twitter.com/0UMwjEcbYP

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Trevor Bedford‏Verified account @trvrb Feb 3

These rates of HA amino acid substitutions mirror experimentally determined rates of antigenic evolution. This is a figure from a 2014 paper by myself, @arambaut and others (https://bedford.io/papers/bedford-flux/ …) showing faster antigenic drift in H3N2 than H1N1 than B/Vic and B/Yam. 12/18pic.twitter.com/EERbr8WduR

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Trevor Bedford‏Verified account @trvrb Feb 3

The rate of antigenic drift in influenza can be quantified by per-year fold-reduction in serological assays. For influenza H3N2, this rate averages ~1 two-fold titer reduction per-year. 13/18

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Trevor Bedford‏Verified account @trvrb Feb 3

Trevor Bedford Retweeted Trevor Bedford

The comparable datapoint for SARS-CoV-2 is work by Wibmer et al (https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1 …) and Cele et al (https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v1 …) showing an ~8-fold titer reduction in neutralization assays to the 501Y.V2 variant from South Africa. 14/18https://twitter.com/trvrb/status/1351785352793493505 …

Trevor Bedford added,

Trevor BedfordVerified account @trvrb

Important new study by Wibmer et al (https://www.biorxiv.org/content/10.1101/2021.01.18.427166v1 …) of neutralization by convalescent sera on wildtype vs 501Y.V2 variant viruses circulating in South Africa. It shows that mutations present in 501Y.V2 result in reduced neutralization capacity. 1/10

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Trevor Bedford‏Verified account @trvrb Feb 3

This titer reduction is very roughly what is seen in an average of 3 years of influenza H3N2 evolution, but yearly jumps of 8-fold titer reductions in H3N2 are historically not uncommon, with H3N2 showing a staccato pace to its antigenic evolution. 15/18

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Trevor Bedford‏Verified account @trvrb Feb 3

Both simple rate of amino acid substitutions in spike S1 and titer drops in serological assays suggest that SARS-CoV-2 might be in the same ballpark as influenza A in terms of capacity for antigenic evolution. 16/18

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Trevor Bedford‏Verified account @trvrb Feb 3

That said, the evolution that we've seen with the recent variants of concern may represent an unusual circumstance in which the virus has made a large evolutionary jump to a new "fitness peak" and that won't be seen year-after-year. 17/18

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Trevor Bedford‏Verified account @trvrb Feb 3

Additionally, with new vaccine technologies (and particularly mRNA vaccines) we'll have the ability to more effectively chase the virus than we do with the seasonal influenza vaccine, which suffers from lower immunogenicity and longer lead times for strain updates. 18/18

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JF‏ @jackfruitstaken Feb 3

Replying to @trvrb

Is there a reason the mRNA vaccines have been tested and approved faster? It makes sense they'd be able to adapt to the spike, since that's what the actual mRNA of the vaccine encodes, but it seems like the regulatory turnaround has been quicker as well, at least in the US.

11:19 AM - 3 Feb 2021

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