@article{4d51b7cbf4a54f0ead335d6084a0b004,
title = "Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination",
abstract = "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.",
keywords = "COVID-19, Fc-function, Fc-receptors, SARS-CoV-2, antibodies, correlates, neutralization, prime-boost, vaccination",
author = "Gorman, {Matthew J.} and Nita Patel and Mimi Guebre-Xabier and Zhu, {Alex L.} and Caroline Atyeo and Pullen, {Krista M.} and Carolin Loos and Yenny Goez-Gazi and Ricardo Carrion and Tian, {Jing Hui} and Dansu Yuan and Bowman, {Kathryn A.} and Bin Zhou and Sonia Maciejewski and McGrath, {Marisa E.} and James Logue and Frieman, {Matthew B.} and David Montefiori and Colin Mann and Sharon Schendel and Fatima Amanat and Florian Krammer and Saphire, {Erica Ollmann} and Lauffenburger, {Douglas A.} and Greene, {Ann M.} and Portnoff, {Alyse D.} and Massare, {Michael J.} and Larry Ellingsworth and Gregory Glenn and Gale Smith and Galit Alter",
note = "Funding Information: This work was funded by Operation Warp Speed . We thank Kathryn Hastie for helpful discussions. We thank Kristal Lam for handling samples and materials for animal studies. We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH research scholars award for their support. We acknowledge support from the Ragon Institute of MGH, MIT and Harvard , the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH ( 3R37AI080289-11S1 , R01AI146785 , U19AI42790-01 , U19AI135995-02 , U19AI42790-02S1 , 1U01CA260476-01 , and CIVIC75N93019C00052 ), National Science Foundation graduate research fellowship grant no. 1745302 , the Gates Foundation Global Health Vaccine Accelerator Platform funding ( OPP1146996 and INV-001650 ), the COVID-19 Therapeutics Accelerator ( INV-006133 ), and the Musk Foundation . Research work in the Krammer laboratory was partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract no. HHSN272201400008C ); by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611 [5384] ); and by anonymous donors . The graphical abstract was created with BioRender.com . Funding Information: This work was funded by Operation Warp Speed. We thank Kathryn Hastie for helpful discussions. We thank Kristal Lam for handling samples and materials for animal studies. We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH research scholars award for their support. We acknowledge support from the Ragon Institute of MGH, MIT and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-02S1, 1U01CA260476-01, and CIVIC75N93019C00052), National Science Foundation graduate research fellowship grant no. 1745302, the Gates Foundation Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), the COVID-19 Therapeutics Accelerator (INV-006133), and the Musk Foundation. Research work in the Krammer laboratory was partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract no. HHSN272201400008C); by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611 [5384]); and by anonymous donors. The graphical abstract was created with BioRender.com. N.P. M.G.-X. Y.G.-G. R.C. J.-H.T. B.Z. M.J.M. A.D.P. M.J.G. C.A. A.L.Z. G.A. C.L. K.M.P. E.O.S. D.L. F.K. and G.S. contributed to conceptualization of experiments, generation of data and analysis, and interpretation of the results. N.P. J.-H.T. B.Z. S.M. Y.G.-G. R.C. C.A. M.J.G. A.L.Z. D.Y. K.A.B. F.A. S.S. M.E.M. J.L. C.M. and M.B.F. performed experiments. N.P. M.G.-X. Y.G.-G. R.C. G.A. and M.B.F. coordinated projects. G.S. G.G. D.L. D.M. M.G.-X. A.M.G. N.P. Y.G.-G. R.C. M.B.F. M.J.G, C.A. G.A. C.L. K.M.P. and L.E. contributed to drafting and making critical revisions with the assistance of others. N.P. M.G.-X. J.-H.T. B.Z. S.M. A.M.G. M.J.M. A.D.P. G.G. G.S. and L.E. are current or past employees of Novavax, Inc. and have stock options in the company. G.A. is the founder of SeromYx Systems, Inc. A.L.Z. is a current employee of Moderna, Inc. but conducted this work before employment. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. F.A. is also listed on the serological assay patent application as a co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Y.G.-G. R.C. M.J.G. C.A. K.M.P. C.L. D.Y. K.A.B. M.E.M. J.L. D.M. C.M. S.S. F.A. E.O.S, D.L. and M.B.F. declare no competing interest. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = sep,
day = "21",
doi = "10.1016/j.xcrm.2021.100405",
language = "English",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "9",
}