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

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.

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 F(C) receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC(50) 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 (3×10(6) 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.