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

John E. Bowen; Young Jun Park; Cameron Stewart; Jack T. Brown; William K. Sharkey; Alexandra C. Walls; Anshu Joshi; Kaitlin R. Sprouse; Matthew McCallum; M. Alejandra Tortorici; Nicholas M. Franko; Jennifer K. Logue; Ignacio G. Mazzitelli; Annalee W. Nguyen; Rui P. Silva; Yimin Huang; Jun Siong Low; Josipa Jerak; Sasha W. Tiles; Kumail Ahmed; Asefa Shariq; Jennifer M. Dan; Zeli Zhang; Daniela Weiskopf; Alessandro Sette; Gyorgy Snell; Christine M. Posavad; Najeeha Talat Iqbal; Jorge Geffner; Alessandra Bandera; Andrea Gori; Federica Sallusto; Jennifer A. Maynard; Shane Crotty; Wesley C. Van Voorhis; Carlos Simmerling; Renata Grifantini; Helen Y. Chu; Davide Corti; David Veesler

doi:10.1126/SCIIMMUNOL.ADF1421

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

John E. Bowen
, Young Jun Park
, Cameron Stewart
, Jack T. Brown
, William K. Sharkey
, Alexandra C. Walls
, Anshu Joshi
, Kaitlin R. Sprouse
, Matthew McCallum
, M. Alejandra Tortorici
, Nicholas M. Franko
, Jennifer K. Logue
, Ignacio G. Mazzitelli
, Annalee W. Nguyen
, Rui P. Silva
, Yimin Huang
, Jun Siong Low
, Josipa Jerak
, Sasha W. Tiles
, Kumail Ahmed

Asefa Shariq, Jennifer M. Dan, Zeli Zhang, Daniela Weiskopf, Alessandro Sette, Gyorgy Snell, Christine M. Posavad, Najeeha Talat Iqbal, Jorge Geffner, Alessandra Bandera, Andrea Gori, Federica Sallusto, Jennifer A. Maynard, Shane Crotty, Wesley C. Van Voorhis, Carlos Simmerling, Renata Grifantini, Helen Y. Chu, Davide Corti, David Veesler

Laufer Center for Physical and Quantitative Biology

University of Washington
Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS)
University of Texas at Austin
Università della Svizzera italiana
Aga Khan University
La Jolla Institute for Allergy and Immunology
University of California at San Diego
Vir Biotechnology, Inc.
Fred Hutchinson Cancer Research Center
IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano
INGM - Fondazione Istituto Nazionale Genetica Molecolare

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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.

Original language	English
Article number	eadf1421
Journal	Science Immunology
Volume	7
Issue number	78
DOIs	https://doi.org/10.1126/SCIIMMUNOL.ADF1421
State	Published - Dec 2022

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Bowen, J. E., Park, Y. J., Stewart, C., Brown, J. T., Sharkey, W. K., Walls, A. C., Joshi, A., Sprouse, K. R., McCallum, M., Tortorici, M. A., Franko, N. M., Logue, J. K., Mazzitelli, I. G., Nguyen, A. W., Silva, R. P., Huang, Y., Low, J. S., Jerak, J., Tiles, S. W., ... Veesler, D. (2022). SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines. Science Immunology, 7(78), Article eadf1421. https://doi.org/10.1126/SCIIMMUNOL.ADF1421

@article{cb4d3f8bdf44470da2c9ad2ed23157d2,

title = "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.",

author = "Bowen, \{John E.\} and Park, \{Young Jun\} and Cameron Stewart and Brown, \{Jack T.\} and Sharkey, \{William K.\} and Walls, \{Alexandra C.\} and Anshu Joshi and Sprouse, \{Kaitlin R.\} and Matthew McCallum and Tortorici, \{M. Alejandra\} and Franko, \{Nicholas M.\} and Logue, \{Jennifer K.\} and Mazzitelli, \{Ignacio G.\} and Nguyen, \{Annalee W.\} and Silva, \{Rui P.\} and Yimin Huang and Low, \{Jun Siong\} and Josipa Jerak and Tiles, \{Sasha W.\} and Kumail Ahmed and Asefa Shariq and Dan, \{Jennifer M.\} and Zeli Zhang and Daniela Weiskopf and Alessandro Sette and Gyorgy Snell and Posavad, \{Christine M.\} and Iqbal, \{Najeeha Talat\} and Jorge Geffner and Alessandra Bandera and Andrea Gori and Federica Sallusto and Maynard, \{Jennifer A.\} and Shane Crotty and \{Van Voorhis\}, \{Wesley C.\} and Carlos Simmerling and Renata Grifantini and Chu, \{Helen Y.\} and Davide Corti and David Veesler",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved;",

year = "2022",

month = dec,

doi = "10.1126/SCIIMMUNOL.ADF1421",

language = "English",

volume = "7",

journal = "Science Immunology",

issn = "2470-9468",

number = "78",

}

Bowen, JE, Park, YJ, Stewart, C, Brown, JT, Sharkey, WK, Walls, AC, Joshi, A, Sprouse, KR, McCallum, M, Tortorici, MA, Franko, NM, Logue, JK, Mazzitelli, IG, Nguyen, AW, Silva, RP, Huang, Y, Low, JS, Jerak, J, Tiles, SW, Ahmed, K, Shariq, A, Dan, JM, Zhang, Z, Weiskopf, D, Sette, A, Snell, G, Posavad, CM, Iqbal, NT, Geffner, J, Bandera, A, Gori, A, Sallusto, F, Maynard, JA, Crotty, S, Van Voorhis, WC, Simmerling, C, Grifantini, R, Chu, HY, Corti, D & Veesler, D 2022, 'SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines', Science Immunology, vol. 7, no. 78, eadf1421. https://doi.org/10.1126/SCIIMMUNOL.ADF1421

TY - JOUR

T1 - SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines

AU - Bowen, John E.

AU - Park, Young Jun

AU - Stewart, Cameron

AU - Brown, Jack T.

AU - Sharkey, William K.

AU - Walls, Alexandra C.

AU - Joshi, Anshu

AU - Sprouse, Kaitlin R.

AU - McCallum, Matthew

AU - Tortorici, M. Alejandra

AU - Franko, Nicholas M.

AU - Logue, Jennifer K.

AU - Mazzitelli, Ignacio G.

AU - Nguyen, Annalee W.

AU - Silva, Rui P.

AU - Huang, Yimin

AU - Low, Jun Siong

AU - Jerak, Josipa

AU - Tiles, Sasha W.

AU - Ahmed, Kumail

AU - Shariq, Asefa

AU - Dan, Jennifer M.

AU - Zhang, Zeli

AU - Weiskopf, Daniela

AU - Sette, Alessandro

AU - Snell, Gyorgy

AU - Posavad, Christine M.

AU - Iqbal, Najeeha Talat

AU - Geffner, Jorge

AU - Bandera, Alessandra

AU - Gori, Andrea

AU - Sallusto, Federica

AU - Maynard, Jennifer A.

AU - Crotty, Shane

AU - Van Voorhis, Wesley C.

AU - Simmerling, Carlos

AU - Grifantini, Renata

AU - Chu, Helen Y.

AU - Corti, Davide

AU - Veesler, David

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85143490129

U2 - 10.1126/SCIIMMUNOL.ADF1421

DO - 10.1126/SCIIMMUNOL.ADF1421

M3 - Article

C2 - 36356052

AN - SCOPUS:85143490129

SN - 2470-9468

VL - 7

JO - Science Immunology

JF - Science Immunology

IS - 78

M1 - eadf1421

ER -

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

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