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

BOWEN, JOHN E.; PARK, YOUNG-JUN; STEWART, CAMERON; BROWN, JACK T.; SHARKEY, WILLIAM K.; WALLS, ALEXANDRA C.; JOSHI, ANSHU; SPROUSE, KAITLIN R.; MCCALLUM, MATTHEW; TORTORICI, M. ALEJANDRA; FRANKO, NICHOLAS M.; LOGUE, JENNIFER K.; MAZZITELLI, IGNACIO G.; NGUYEN, ANNALEE W.; SILVA, RUI P.; HUANG, YIMIN; LOW, JUN SIONG; JERAK, JOSIPA; TILES, SASHA W.; AHMED, KUMAIL; SHARIQ, ASEFA; DAN, JENNIFER M.; ZHANG, ZELI; WEISKOPF, DANIELA; SETTE, ALESSANDRO; SNELL, GYORGY; POSAVAD, CHRISTINE M.; IQBAL, NAJEEHA TALAT; GEFFNER, JORGE; BANDERA, ALESSANDRA; GORI, ANDREA; SALLUSTO, FEDERICA; MAYNARD, JENNIFER A.; CROTTY, SHANE; VAN VOORHIS, WESLEY C.; SIMMERLING, CARLOS; GRIFANTINI, RENATA; CHU, HELEN Y.; CORTI, DAVIDE; VEESLER, DAVID

Science Immunology

American Association for the Advancement of Science

Año: 2022 vol. 7

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.