Cell Reports Medicine (Sep 2021)
Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination
- Matthew J. Gorman,
- Nita Patel,
- Mimi Guebre-Xabier,
- Alex L. Zhu,
- Caroline Atyeo,
- Krista M. Pullen,
- Carolin Loos,
- Yenny Goez-Gazi,
- Ricardo Carrion, Jr.,
- 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 Saphire,
- Douglas A. Lauffenburger,
- Ann M. Greene,
- Alyse D. Portnoff,
- Michael J. Massare,
- Larry Ellingsworth,
- Gregory Glenn,
- Gale Smith,
- Galit Alter
Affiliations
- Matthew J. Gorman
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Nita Patel
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Mimi Guebre-Xabier
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Alex L. Zhu
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Virology and Immunology Program, University of Duisburg-Essen, Essen, Germany
- Caroline Atyeo
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Krista M. Pullen
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Carolin Loos
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Yenny Goez-Gazi
- Texas Biomedical Research Institute, 8715 West Military Drive, San Antonio, TX 78227, USA
- Ricardo Carrion, Jr.
- Texas Biomedical Research Institute, 8715 West Military Drive, San Antonio, TX 78227, USA
- Jing-Hui Tian
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Dansu Yuan
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Kathryn A. Bowman
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Bin Zhou
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Sonia Maciejewski
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Marisa E. McGrath
- University of Maryland School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA
- James Logue
- University of Maryland School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA
- Matthew B. Frieman
- University of Maryland School of Medicine, 685 West Baltimore St, Baltimore, MD 21201, USA
- David Montefiori
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
- Colin Mann
- La Jolla Institute for Immunology, La Jolla, CA 92037, USA
- Sharon Schendel
- La Jolla Institute for Immunology, La Jolla, CA 92037, USA
- Fatima Amanat
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Florian Krammer
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Erica Ollmann Saphire
- La Jolla Institute for Immunology, La Jolla, CA 92037, USA
- Douglas A. Lauffenburger
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Ann M. Greene
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Alyse D. Portnoff
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Michael J. Massare
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Larry Ellingsworth
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Gregory Glenn
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA
- Gale Smith
- Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD 20878, USA; Corresponding author
- Galit Alter
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Corresponding author
- Journal volume & issue
-
Vol. 2,
no. 9
p. 100405
Abstract
Summary: 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.
