Thread by @abrahamlabhms

Excited to share our manuscript just published @ScienceMagazine describing mechanisms for continued antibody evasion of the SARS-CoV-2 RBD. Hopefully, the findings help us better prepare for #Omicron.
science.org/doi/10.1126/sc…

Most prior studies examined RBD escape mutations in isolation or in small numbers, but we studied variants that contain many simultaneous spike protein mutations (e.g., RBD mutations at K417, T478, E484, Y489, Q493, S494, and N501, and NTD deletions).

Takeaways include:
Structural plasticity allows a SARS-CoV-2 RBD containing multiple antibody escape mutations that evolved in an immunocompromised host to bind tightly to human ACE2

As the virus adapts to escape human antibody responses, RBDs with many mutations could evolve to still bind ACE2. Using non-infectious virus-like particles (pseudotypes), we found that highly mutated variants could escape neutralization by monoclonal antibodies in clinical use.

All recipients of mRNA vaccines we tested had some detectable serum neutralizing activity post second vaccine dose
There was significant but incomplete loss of serum neutralizing activity against variants with highly mutated spike proteins

The quality, quantity, and epitope breadth of antibodies elicited by mRNA vaccination (or in principle through boosting as immunity wanes) with the original vaccine may provide some level of neutralizing activity against highly mutated variants

Thanking all awesome collaborators on this work @mgh_id @bwh_id @MassCPR @neidl @VirologyHarvard @HarvardMicro

And lastly, also thanking superstar @HarvardMITmdphd student @katherine_nabel, lab alumn @SarahA_Clark, and all other labs members.