Selective SARS-CoV2 BA.2 escape of antibody Fc/Fc-receptor interactions

The number of mutations in the omicron (B.1.1.529) BA.1 variant of concern led to an unprecedented evasion of vaccine induced immunity. However, despite rise in global infections, severe disease did not increase proportionally and is likely linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of new sublineage BA.2, which is more transmissible than BA.1 despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine-induced responses. Here, we comprehensively profiled the BNT162b2 vaccine-induced response to several VOCs, including omicron BA.1 and BA.2. While vaccine-induced immune responses were compromised against both omicron sublineages, vaccine-induced antibody isotype titers, and non-neutralizing Fc effector functions were attenuated to the omicron BA.2 spike compared to BA.1. Conversely, Fc gamma R2a and Fc gamma R2b binding was elevated to BA. 2, albeit lower than BA.1 responses, potentially contributing to persistent protection against severity of disease.

Automated summary

The omicron (B.1.1.529) BA.1 variant has mutations that evade vaccine immunity, but severe disease is still relatively low due to T cell recognition and non-neutralizing antibodies. However, the BA.2 sublineage, which is more transmissible, may evade some vaccine-induced responses. This study found that vaccine-induced immune responses were compromised against both omicron sublineages, but non-neutralizing Fc effector functions were attenuated more in BA.2 compared to BA.1.