Adjuvanted SARS-CoV-2 spike protein elicits neutralizing antibodies and CD4 T cell responses after a single immunization in mice

EBioMedicine. 2021 Jan:63:103197. doi: 10.1016/j.ebiom.2020.103197. Epub 2021 Jan 7.

Abstract

Background: SARS-CoV-2 has caused a global pandemic, infecting millions of people. A safe, effective vaccine is urgently needed and remains a global health priority. Subunit vaccines are used successfully against other viruses when administered in the presence of an effective adjuvant.

Methods: We evaluated three different clinically tested adjuvant systems in combination with the SARS-CoV-2 pre-fusion stabilized (S-2P) spike protein using a one-dose regimen in mice.

Findings: Whilst spike protein alone was only weakly immunogenic, the addition of either Aluminum hydroxide, a squalene based oil-in-water emulsion system (SE) or a cationic liposome-based adjuvant significantly enhanced antibody responses against the spike receptor binding domain (RBD). Kinetics of antibody responses differed, with SE providing the most rapid response. Neutralizing antibodies developed after a single immunization in all adjuvanted groups with ID50 titers ranging from 86-4063. Spike-specific CD4 T helper responses were also elicited, comprising mainly of IFN-γ and IL-17 producing cells in the cationic liposome adjuvanted group, and more IL-5- and IL-10-secreting cells in the AH group.

Interpretation: These results demonstrate that adjuvanted spike protein subunit vaccine is a viable strategy for rapidly eliciting SARS-CoV-2 neutralizing antibodies and CD4 T cell responses of various qualities depending on the adjuvant used, which can be explored in further vaccine development against COVID-19.

Funding: This work was supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.

Keywords: Alum; CAF®01; MF59(TM); Neutralizing antibodies; SARS-CoV-2; Squalene emulsion; Subunit vaccine.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry
  • Aluminum Hydroxide / chemistry
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / metabolism*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / metabolism*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • COVID-19 / pathology
  • COVID-19 / virology
  • Female
  • Immunization
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Liposomes / chemistry
  • Mice
  • Mice, Inbred C57BL
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*
  • Squalene / chemistry
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Interleukin-17
  • Liposomes
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Subunit
  • spike protein, SARS-CoV-2
  • Aluminum Hydroxide
  • Squalene
  • Interferon-gamma