Immunization with synthetic SARS-CoV-2 S glycoprotein virus-like particles protects macaques from infection

Cell Rep Med. 2022 Jan 24;3(2):100528. doi: 10.1016/j.xcrm.2022.100528. eCollection 2022 Feb 15.


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused an ongoing global health crisis. Here, we present as a vaccine candidate synthetic SARS-CoV-2 spike (S) glycoprotein-coated lipid vesicles that resemble virus-like particles. Soluble S glycoprotein trimer stabilization by formaldehyde cross-linking introduces two major inter-protomer cross-links that keep all receptor-binding domains in the "down" conformation. Immunization of cynomolgus macaques with S coated onto lipid vesicles (S-LVs) induces high antibody titers with potent neutralizing activity against the vaccine strain, Alpha, Beta, and Gamma variants as well as T helper (Th)1 CD4+-biased T cell responses. Although anti-receptor-binding domain (RBD)-specific antibody responses are initially predominant, the third immunization boosts significant non-RBD antibody titers. Challenging vaccinated animals with SARS-CoV-2 shows a complete protection through sterilizing immunity, which correlates with the presence of nasopharyngeal anti-S immunoglobulin G (IgG) and IgA titers. Thus, the S-LV approach is an efficient and safe vaccine candidate based on a proven classical approach for further development and clinical testing.

Keywords: B cells; COVID-19; S glycoprotein; SARS-CoV-2; antibodies; formaldehyde cross-linking; immunity; macaques; nanoparticles; protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • COVID-19 / epidemiology
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / immunology
  • Chlorocebus aethiops
  • Disease Models, Animal
  • HEK293 Cells
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Liposomes
  • Macaca fascicularis
  • Male
  • Pandemics / prevention & control
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Th1 Cells / immunology
  • Treatment Outcome
  • Vaccination / methods*
  • Vaccines, Virus-Like Particle / administration & dosage*
  • Vaccines, Virus-Like Particle / immunology
  • Vero Cells


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Liposomes
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Virus-Like Particle
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants