Reduced neutralization and Fc effector function to Omicron subvariants in sera from SARS-CoV-1 survivors after two doses of CoronaVac plus one dose subunit vaccine

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross-clade pan-sarbecovirus neutralizing antibodies in survivors of the infection by SARS-CoV-1, the neutralization activity and Fc-mediated effector functions of these cross-reactive antibodies elicited in SARS-CoV-1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc-mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS-CoV-1 convalescents and healthy individuals. Potent cross-clade broadly neutralizing antibodies were observed in SARS-CoV-1 survivors who received a three-dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS-CoV-1 infection may exacerbate the impairment of neutralization activity and Fc-mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future.

Keywords: ADCC and ADCP; Omicron; SARS-CoV-1; SARS-CoV-2 VOCs; immune imprinting; neutralizing antibodies.