Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Young-Jun Park,et al.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination.We show that hybrid immunity or vaccine boosters elicit plasma neutralizing activity against Omicron BA.1,BA.2,BA.2.12.1 and BA.4/5 and that breakthrough infections,but not vaccination-only,induce neutralizing activity in the nasal mucosa.Consistent with immunological imprinting,most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1,BA.1,BA.2,and BA.4/5 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months post infection.Although most clinical antibodies have reduced neutralization of Omicron,we identified an ultrapotent pan-variant neutralizing antibody,that is a strong candidate for clinical development.