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- Title
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines.
- Authors
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
- 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.
- Publication
Science Immunology, 2022, Vol 7, Issue 78, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adf1421