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.
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines / J.E. Bowen, Y. Park, C. Stewart, J.T. Brown, W.K. Sharkey, A.C. Walls, A. Joshi, K.R. Sprouse, M. Mccallum, M.A. Tortorici, N.M. Franko, J.K. Logue, I.G. Mazzitelli, A.W. Nguyen, R.P. Silva, Y. Huang, J.S. Low, J. Jerak, S.W. Tiles, K. Ahmed, A. Shariq, J.M. Dan, Z. Zhang, D. Weiskopf, A. Sette, G. Snell, C.M. Posavad, N.T. Iqbal, J. Geffner, A. Bandera, A. Gori, F. Sallusto, J.A. Maynard, S. Crotty, W.C. Van Voorhis, C. Simmerling, R. Grifantini, H.Y. Chu, D. Corti, D. Veesler. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 7:78(2022 Dec 23), pp. eadf1421.1-eadf1421.15. [10.1126/sciimmunol.adf1421]
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines
A. Bandera;A. Gori;
2022
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.
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