Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after 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; O039,; 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; Boyoglu-Barnum, Seyhan; Van De Wetering, Renee; Tylor, Alida; McCarthy, Elizabeth; Lecouturier, Valerie; Ruiz, Sophie; Berry, Catherine; Tibbitts, Timothy; Andersen, Hanne; Cook, Anthony; Dodson, Alan; Pessaint, Laurent; Van Ry, Alex; 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

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 protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 106 plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein-specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.