Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-Mâ„¢ vaccination

Gorman, Matthew J.; Patel, Nita; Guebre-Xabier, Mimi; Zhu, Alex L.; Atyeo, Caroline; Pullen, Krista M.; Loos, Carolin; Goez-Gazi, Yenny; Carrion, Ricardo; Tian, Jing-Hui; Yuan, Dansu; Bowman, Kathryn A.; Zhou, Bin; Maciejewski, Sonia; McGrath, Marisa E.; Logue, James; Frieman, Matthew B.; Montefiori, David; Mann, Colin; Schendel, Sharon; Amanat, Fatima; Krammer, Florian; Saphire, Erica Ollmann; Lauffenburger, Douglas; Greene, Ann M.; Portnoff, Alyse D.; Massare, Michael J.; Ellingsworth, Larry; Glenn, Gregory; Smith, Gale; Alter, Galit

Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2 associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining correlates of immunity across a spectrum of antibody titers is urgently required. Thus, we profiled the humoral immune response in a cohort of non-human primates immunized with a recombinant SARS-CoV-2 spike glycoprotein (NVX-CoV2373) at two doses, administered as a single or two-dose regimen. Both antigen dose and boosting significantly altered neutralization titers and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints Combined differences in antibody effector functions and neutralization were associated with distinct levels of protection in the upper and lower respiratory tract. Moreover, NVX-CoV2373 elicited antibodies that functionally targeted emerging SARS-CoV-2 variants. Collectively, the data presented here suggest that a single dose may prevent disease via combined Fc/Fab functions, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.