RT Journal Article
SR Electronic
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
FD Cold Spring Harbor Laboratory
SP 2021.03.02.433390
DO 10.1101/2021.03.02.433390
A1 Joseph R. Francica
A1 Barbara J. Flynn
A1 Kathryn E. Foulds
A1 Amy T. Noe
A1 Anne P. Werner
A1 Ian N. Moore
A1 Matthew Gagne
A1 Timothy S. Johnston
A1 Courtney Tucker
A1 Rachel L. Davis
A1 Britta Flach
A1 Sarah O’Connell
A1 Shayne F. Andrew
A1 Evan Lamb
A1 Dillon R. Flebbe
A1 Saule T. Nurmukhambetova
A1 Mitzi M. Donaldson
A1 John-Paul M. Todd
A1 Alex Lee Zhu
A1 Caroline Atyeo
A1 Stephanie Fischinger
A1 Matthew J Gorman
A1 Sally Shin
A1 Venkata Viswanadh Edara
A1 Katharine Floyd
A1 Lilin Lai
A1 Alida Tylor
A1 Elizabeth McCarthy
A1 Valerie Lecouturier
A1 Sophie Ruiz
A1 Catherine Berry
A1 Timothy Tibbitts
A1 Hanne Andersen
A1 Anthony Cook
A1 Alan Dodson
A1 Laurent Pessaint
A1 Alex Van Ry
A1 Marguerite Koutsoukos
A1 Cindy Gutzeit
A1 I-Ting Teng
A1 Tongqing Zhou
A1 Dapeng Li
A1 Barton F. Haynes
A1 Peter D. Kwong
A1 Adrian McDermott
A1 Mark G. Lewis
A1 Tong Ming Fu
A1 Roman Chicz
A1 Robbert van der Most
A1 Kizzmekia S. Corbett
A1 Mehul S. Suthar
A1 Galit Alter
A1 Mario Roederer
A1 Nancy J. Sullivan
A1 Daniel C. Douek
A1 Barney S. Graham
A1 Danilo Casimiro
A1 Robert A. Seder
YR 2021
UL http://biorxiv.org/content/early/2021/03/02/2021.03.02.433390.abstract
AB 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.