PT  - JOURNAL ARTICLE
AU  - Matthew J Gorman
AU  - Nita Patel
AU  - Mimi Guebre-Xabier
AU  - Alex Zhu
AU  - Caroline Atyeo
AU  - Krista M. Pullen
AU  - Carolin Loos
AU  - Yenny Goez-Gazi
AU  - Ricardo Carrion, Jr
AU  - Jing-Hui Tian
AU  - Dansu Yaun
AU  - Kathryn Bowman
AU  - Bin Zhou
AU  - Sonia Maciejewski
AU  - Marisa E. McGrath
AU  - James Logue
AU  - Matthew B. Frieman
AU  - David Montefiori
AU  - Colin Mann
AU  - Sharon Schendel
AU  - Fatima Amanat
AU  - Florian Krammer
AU  - Erica Ollmann Saphire
AU  - Douglas Lauffenburger
AU  - Ann M. Greene
AU  - Alyse D. Portnoff
AU  - Michael J. Massare
AU  - Larry Ellingsworth
AU  - Gregory Glenn
AU  - Gale Smith
AU  - Galit Alter
TI  - Collaboration between the Fab and Fc contribute to maximal protection against SARS-CoV-2 in nonhuman primates following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination
AID  - 10.1101/2021.02.05.429759
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.05.429759
4099  - http://biorxiv.org/content/early/2021/02/05/2021.02.05.429759.short
4100  - http://biorxiv.org/content/early/2021/02/05/2021.02.05.429759.full
AB  - Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™. While antigen dose had some effect on Fc-effector profiles, both antigen dose and boosting significantly altered overall titers, neutralization and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were strongly associated with distinct levels of protection in the upper and lower respiratory tract, pointing to the presence of combined, but distinct, compartment-specific neutralization and Fc-mechanisms as key determinants of protective immunity against infection. Moreover, NVX-CoV2373 elicited antibodies functionally target emerging SARS-CoV-2 variants, collectively pointing to the critical collaborative role for Fab and Fc in driving maximal protection against SARS-CoV-2. Collectively, the data presented here suggest that a single dose may prevent disease, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.HighlightsNVX-CoV2373 subunit vaccine elicits receptor blocking, virus neutralizing antibodies, and Fc-effector functional antibodies.The vaccine protects against respiratory tract infection and virus shedding in non-human primates (NHPs).Both neutralizing and Fc-effector functions contribute to protection, potentially through different mechanisms in the upper and lower respiratory tract.Both macaque and human vaccine-induced antibodies exhibit altered Fc-receptor binding to emerging mutants.Competing Interest StatementNP, MGX, JHT, BZ, SM, AMG, MJM, ADP, GG, GS, and LE are current or past employees of Novavax, Inc. and have stock options in the company. GA is the founder of SeromYx Systems, Inc. AZ is a current employee of Moderna, Inc. but conducted this work before employment. YG, RC, JD, EC, MG, HMS, CB, JDC, KA, MJG, CA, KMP, CL, DY, KB, MEM, JL, DM, CM, SS, FA, FK, EOS, DL, and MBF declare no competing interest.