1. Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates
- Author
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Anthony L. Cook, Hanne Leth Andersen, John-Paul Todd, Sophie Ruiz, Katharine Floyd, Tongqing Zhou, Evan Lamb, Shayne F. Andrew, Britta Flach, Sally Shin, Timothy S. Johnston, Catherine C. Berry, Sarah O’Connell, Nancy J. Sullivan, Joseph R. Francica, Stephanie Fischinger, Alida Tylor, Dapeng Li, Kathryn E. Foulds, Daniel C. Douek, Robert A. Seder, Alex Lee Zhu, Ian N. Moore, Rachel L. Davis, Roman Chicz, Mark G. Lewis, Courtney Tucker, Alex Van Ry, Elizabeth McCarthy, Barney S. Graham, Marguerite Koutsoukos, Robbert van der Most, I.-Ting Teng, Amy T. Noe, Cindy Gutzeit, Matthew Gagne, Mitzi M. Donaldson, Alan Dodson, Tong-Ming Fu, Saule T. Nurmukhambetova, Laurent Pessaint, Venkata Viswanadh Edara, Adrian B. McDermott, Renee van de Wetering, Kizzmekia S. Corbett, Peter D. Kwong, Danilo Casimiro, Timothy Tibbitts, Barbara J. Flynn, Seyhan Boyoglu-Barnum, Valerie Lecouturier, Matthew J. Gorman, Anne P. Werner, Dillon R. Flebbe, Mehul S. Suthar, Mario Roederer, Lilin Lai, Caroline Atyeo, Barton F. Haynes, and Galit Alter
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Primates ,0301 basic medicine ,medicine.medical_treatment ,Medizin ,Antibodies, Viral ,medicine.disease_cause ,Immunoglobulin G ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cricetinae ,medicine ,Animals ,030212 general & internal medicine ,AS03 ,Lung ,COVID-19 Serotherapy ,Coronavirus ,biology ,SARS-CoV-2 ,business.industry ,Vaccination ,Immunization, Passive ,COVID-19 ,General Medicine ,Antibodies, Neutralizing ,Virology ,030104 developmental biology ,Spike Glycoprotein, Coronavirus ,biology.protein ,Antibody ,business ,Adjuvant - 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.
- Published
- 2021
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