Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques

Nat Commun. 2021 Mar 3;12(1):1403. doi: 10.1038/s41467-021-21665-8.

Abstract

SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibody Formation / physiology
  • COVID-19 Vaccines / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Macaca
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • SARS-CoV-2 / pathogenicity*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Viral Vaccines / therapeutic use

Substances

  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Viral Vaccines