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

Cell Rep Med. 2021 Sep 21;2(9):100405. doi: 10.1016/j.xcrm.2021.100405. Epub 2021 Aug 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / drug effects
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • COVID-19 / immunology
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • Dose-Response Relationship, Immunologic
  • Female
  • Immunity, Humoral / immunology
  • Immunogenicity, Vaccine
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fc Fragments / immunology
  • Macaca mulatta
  • Male
  • Nanoparticles
  • Primates / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Saponins / immunology*
  • Spike Glycoprotein, Coronavirus
  • Vaccination


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fc Fragments
  • Matrix-M
  • Saponins
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • NVX-CoV2373 adjuvated lipid nanoparticle

Supplementary concepts

  • SARS-CoV-2 variants