Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates
| Autor: | Alex Van Ry, Mark G. Lewis, Alida Tylor, Amy T. Noe, Kathryn E. Foulds, I-Ting Teng, Mitzi M. Donaldson, Peter D. Kwong, Evan Lamb, Britta Flach, Barney S. Graham, Matthew Gagne, Timothy S. Johnston, Robert A. Seder, Venkata Viswanadh Edara, Barbara J. Flynn, Cindy Gutzeit, Hanne Leth Andersen, Joseph R. Francica, Lilin Lai, Tong-Ming Fu, Alex Lee Zhu, Roman Chicz, Alan Dodson, Danilo Casimiro, Sally Shin, Rachel L. Davis, Shayne F. Andrew, Saule T. Nurmukhambetova, Elizabeth McCarthy, Kizzmekia S. Corbett, Dillon R. Flebbe, Tongqing Zhou, Laurent Pessaint, Stephanie Fischinger, Courtney Tucker, Matthew J. Gorman, Nancy J. Sullivan, Anthony L. Cook, Dapeng Li, Adrian B. McDermott, Katharine Floyd, Anne P. Werner, Caroline Atyeo, Barton F. Haynes, Mehul S. Suthar, Galit Alter, Ian N. Morre, Daniel C. Douek, Timothy Tibbitts, John-Paul Todd, Marguerite Koutsoukos, Robbert van der Most |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | bioRxiv article-version (status) pre article-version (number) 1 |
| Popis: | 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 trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FCreceptors mediating effector functionsin vitro. Pseudovirus and live virus neutralizing IC50titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×106PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials. |
| Databáze: | OpenAIRE |
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