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

• DOI: 10.1016/j.xcrm.2021.100405
• Publication Date: 2021-08-31T06:25:05Z
• Authors: Matthew J. Gorman; Nita Patel; Mimi Guebre-Xabier; Alex L. Zhu; Caroline Atyeo; Krista M. Pullen; Carolin Loos; Yenny Goez-Gazi; Ricardo Carrion; Jing-Hui Tian; Dansu Yuan; Kathryn A. Bowman; Bin Zhou; Sonia Maciejewski; Marisa E. McGrath; James Logue; Matthew B. Frieman; David Montefiori; Colin Mann; Sharon Schendel; Fatima Amanat; Florian Krammer; Erica Ollmann Sap...; Douglas A. Lauffe...; Ann M. Greene; Alyse D. Portnoff; Michael J. Massare; Larry Ellingsworth; Gregory Glenn; Gale Smith; Galit Alter
• Keywords: Male; Primates; Medicine (General); Fc-receptors; COVID-19 Vaccines; Medizin; Dose-Response Relationship, Immunologic; Antibodies, Viral; Article; Immunoglobulin Fab Fragments; 03 medical and health sciences; R5-920; Immunogenicity, Vaccine; antibodies; Animals; 0303 health sciences; Fc-function; SARS-CoV-2; Vaccination; COVID-19; correlates; Saponins; vaccination; Antibodies, Neutralizing; Macaca mulatta; Immunity, Humoral; Immunoglobulin Fc Fragments; 3. Good health; Spike Glycoprotein, Coronavirus; Nanoparticles; Female

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 the 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.