Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates

• Type of Material: Article
• Authors: Joseph R Francica, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Barbara J Flynn, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Kathryn E Foulds, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Amy T Noe, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Anne P Werner, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Ian Moore, Emory University; Matthew Gagne, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Timothy S Johnston, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Courtney Tucker, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Rachel L Davis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Britta Flach, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Sarah O'Connell, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Shayne F Andrew, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Evan Lamb, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Dillon R Flebbe, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Saule T Nurmukhambetova, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Mitzi M Donaldson, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; John-Paul M Todd, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Alex Lee Zhu, MIT; Caroline Atyeo, MIT; Stephanie Fischinger, MIT; Matthew J Gorman, MIT; Sally Shin, MIT; Venkata Viswanadh Edara, Childrens Healthcare Atlanta & Emory Univ; Katharine Floyd, Childrens Healthcare Atlanta & Emory Univ; Lilin Lai, Emory University; Seyhan Boyoglu-Barnum, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Renee Van de Wetering, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Alida Tylor, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Elizabeth McCarthy, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Valerie Lecouturier, Sanofi Pasteur; Sophie Ruiz, Sanofi Pasteur; Catherine Berry, Sanofi Pasteur; Timothy Tibbitts, Sanofi Pasteur; Hanne Andersen, BIOQUAL Inc.; Anthony Cook, BIOQUAL Inc.; Alan Dodson, BIOQUAL Inc.; Laurent Pessaint, BIOQUAL Inc.; Alex Van Ry, BIOQUAL Inc.; Marguerite Koutsoukos, GSK; Cindy Gutzeit, GSK; I-Ting Teng, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Tongqing Zhou, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Dapeng Li, Duke University; Barton F Haynes, Duke University; Peter D Kwong, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Adrian McDermott, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Mark G Lewis, BIOQUAL Inc.; Tong Ming Fu, Sanofi Pasteur; Roman Chicz, Sanofi Pasteur; Robert van der Most, GSK; Kizzmekia S Corbett, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Mehul Suthar, Emory University; Galit Alter, MIT; Mario Roederer, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Nancy J Sullivan, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Daniel C Douek, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Barney S Graham, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; Danilo Casimiro, Sanofi Pasteur; Robert A Seder, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
• Language: English
• Date: 2021-08-18
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/scitranslmed.abi4547
• Title of Journal or Parent Work: SCIENCE TRANSLATIONAL MEDICINE
• Volume: 13
• Issue: 607
• Grant/Funding Information: Funding was provided in part by the National Institutes of Health (NIH) Intramural Research Program, Sanofi Pasteur, and the U.S. government through Biomedical Advanced Research and Development Authority (BARDA) under contract HHSO100201600005I to Sanofi Pasteur
• Keywords: Life Sciences & Biomedicine; Cell Biology; IMMUNE-RESPONSES; DOUBLE-BLIND; Science & Technology; Medicine, Research & Experimental; SAFETY; HIGH-THROUGHPUT; SYNCYTIAL VIRUS-VACCINE; Research & Experimental Medicine; IMMUNIZATION; SUBUNIT VACCINE; PANDEMIC INFLUENZA VACCINE; IMMUNOGENICITY; GLYCOPROTEIN
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 106 plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein-specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.