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

Author:

Bowen John E.1ORCID,Park Young-Jun12,Stewart Cameron1ORCID,Brown Jack T.1,Sharkey William K.1,Walls Alexandra C.12ORCID,Joshi Anshu1,Sprouse Kaitlin R.1ORCID,McCallum Matthew1,Tortorici M. Alejandra1ORCID,Franko Nicholas M.3ORCID,Logue Jennifer K.3ORCID,Mazzitelli Ignacio G.4ORCID,Nguyen Annalee W.5,Silva Rui P.5,Huang Yimin5,Low Jun Siong6,Jerak Josipa6,Tiles Sasha W.7ORCID,Ahmed Kumail8ORCID,Shariq Asefa8ORCID,Dan Jennifer M.910,Zhang Zeli910,Weiskopf Daniela910,Sette Alessandro910,Snell Gyorgy11ORCID,Posavad Christine M.12,Iqbal Najeeha Talat8ORCID,Geffner Jorge4ORCID,Bandera Alessandra13ORCID,Gori Andrea13ORCID,Sallusto Federica6,Maynard Jennifer A.5,Crotty Shane910,Van Voorhis Wesley C.7ORCID,Simmerling Carlos1415,Grifantini Renata16ORCID,Chu Helen Y.3ORCID,Corti Davide17ORCID,Veesler David12ORCID

Affiliation:

1. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

2. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

3. Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98195, USA.

4. Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Facultad de Medicina, Buenos Aires C1121ABG, Argentina.

5. McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.

6. Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.

7. Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

8. Departments of Paediatrics and Child Health and Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan.

9. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

10. Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA UC92037, USA.

11. Vir Biotechnology, San Francisco, CA 94158, USA.

12. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

13. Infectious Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.

14. Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.

15. Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY 11794, USA.

16. INGM, Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi,” 20122 Milan, Italy.

17. Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.

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 S 1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S 1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S 1 -directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S 1 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine,Immunology

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