Biology

Virology

Immunity

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Neutralizing antibody

Environmental health

Coronavirus disease 2019 (COVID-19)

Immunology

Monoclonal antibody

Immune system

Vaccination

Convalescent plasma

Population

Infectious disease (medical specialty)

Medicine

Polyclonal antibodies

Virus

Disease

Antibody

Neutralization

Pathology

Proceedings of the National Academy of Sciences

Significance This work shows that, under strong immune pressure, SARS-CoV-2 can use mutations in both the N-terminal domain and the receptor-binding domain to escape potent polyclonal neutralizing responses. Indeed, after a long period under immune selective pressure, SARS-CoV-2 evolved to evade the immunity of a potent polyclonal serum from a COVID-19 convalescent donor. Only three mutations were sufficient to generate this escape variant. The new virus was resistant to 70% of the neutralizing antibodies tested and had a decreased susceptibility to all convalescent sera. Our data predict that, as the immunity in the population increases, following infection and vaccination, new variants will emerge, and therefore vaccines and monoclonal antibodies need to be developed to address them.

SARS-CoV-2 escape from a highly neutralizing COVID-19 convalescent plasma