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