Tony's Diary Package — page 594

Here is an overview first. Will share detailed organized data in a couple of days. I am available to chat at a mutually convenient time. Patrick Vallance from the UK is reaching out to me to get preliminary results as well. We have constructed SARS-CoV-2 pseudoviruses that contain all 8 mutations in the UK variant and all 9 mutations in the SA variant. In addition, we have also constructed pseudoviruses that contain each of the 16 mutations (501Y mutation is shared) individually. This entire panel has been tested on a collection of ~30 spikespecific neutralizing monoclonal antibodies, 20 convalescent plasma, and 18 vaccinee sera (Moderna and Pfizer). First, both UKdelta8 and SAdelta9 showed increased replication capacity in vitro, which is consistent with their increased transmissibility in vivo. Overall, the impact on virus neutralization is profound, with the SA variant being worse than the UK variant. It is quite clear that these two variants could now resist several classes of neutralizing monoclonal antibodies already used in the clinic or still in development, and in most cases we understand which of the mutations are conferring the resistance. This information is particularly relevant to companies like Lilly and Regeneron, which have approved clinical products that are severely affected by these results. In addition, a large majority of convalescent plasma samples showed an appreciable loss in activity against the new variants, suggesting re-infection may be more likely when confronted with either of these two strains. Finally, we also observed a significant impact on vaccinee sera in that every serum sample tested showed a substantial loss in neutralizing activity against the SA variant, whereas the loss in activity against the UK virus is not as large or as universal. Again, we believe the latter findings should be shared promptly with the field, because these new strains threaten the effectiveness of the current vaccines. Importantly, the strategy that the UK is now contemplating (giving one dose and delaying the second dose) is quite dangerous in that one or two additional critical mutations on top of either strain (under suboptimal antibody concentrations induced by one shot without a booster) could render current monoclonal antibodies and vaccines useless. Our data are germane to that debate. Our data are more or less complete, except for live virus neutralization results. We are still waiting for the UK and SA to be distributed by the US government to our lab. We expect to have the live viruses soon, and could generate the confirmatory results in about 7-10 days after receiving the viruses.