TY - JOUR T1 - 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 JF - bioRxiv DO - 10.1101/2021.03.02.433390 SP - 2021.03.02.433390 AU - Joseph R. Francica AU - Barbara J. Flynn AU - Kathryn E. Foulds AU - Amy T. Noe AU - Anne P. Werner AU - Ian N. Moore AU - Matthew Gagne AU - Timothy S. Johnston AU - Courtney Tucker AU - Rachel L. Davis AU - Britta Flach AU - Sarah O’Connell AU - Shayne F. Andrew AU - Evan Lamb AU - Dillon R. Flebbe AU - Saule T. Nurmukhambetova AU - Mitzi M. Donaldson AU - John-Paul M. Todd AU - Alex Lee Zhu AU - Caroline Atyeo AU - Stephanie Fischinger AU - Matthew J Gorman AU - Sally Shin AU - Venkata Viswanadh Edara AU - Katharine Floyd AU - Lilin Lai AU - Alida Tylor AU - Elizabeth McCarthy AU - Valerie Lecouturier AU - Sophie Ruiz AU - Catherine Berry AU - Timothy Tibbitts AU - Hanne Andersen AU - Anthony Cook AU - Alan Dodson AU - Laurent Pessaint AU - Alex Van Ry AU - Marguerite Koutsoukos AU - Cindy Gutzeit AU - I-Ting Teng AU - Tongqing Zhou AU - Dapeng Li AU - Barton F. Haynes AU - Peter D. Kwong AU - Adrian McDermott AU - Mark G. Lewis AU - Tong Ming Fu AU - Roman Chicz AU - Robbert van der Most AU - Kizzmekia S. Corbett AU - Mehul S. Suthar AU - Galit Alter AU - Mario Roederer AU - Nancy J. Sullivan AU - Daniel C. Douek AU - Barney S. Graham AU - Danilo Casimiro AU - Robert A. Seder Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/02/2021.03.02.433390.abstract N2 - 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 FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 titers 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 (3×106 PFU) 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.Competing Interest StatementAll authors have declared the following interests: VL, TB, CB, SR, TMF, DC, RC are Sanofi Pasteur employees and may hold stock. MK, RvdM, and CG are employees of the GSK group of companies and report ownership of GSK shares. ER -