SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines.

ABSTRACT: Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S₁ subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S₁ antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S₁-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S₁ subunit and that variant cross-neutralization is mediated solely by receptor binding domain-specific antibodies. Our data provide a quantitative framework for guiding future S engineering efforts to develop vaccines with higher resilience to the emergence of variants than current technologies.

SUBMITTER: Bowen JE 

PROVIDER: S-EPMC9765460 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature