SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses

Cell Rep Med. 2021 Apr 20;2(4):100252. doi: 10.1016/j.xcrm.2021.100252. Epub 2021 Apr 5.


The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

Keywords: SARS-CoV-2; neutralizing antibodies; protein subunit vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood
  • COVID-19 / prevention & control
  • COVID-19 / veterinary
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology
  • Female
  • Macaca mulatta
  • Male
  • Memory B Cells / immunology
  • Memory B Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Protein Domains / immunology
  • Protein Subunits / immunology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Time Factors
  • Vaccination


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Protein Subunits
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2