Design of the conserved epitope peptide of SARS-CoV-2 spike protein as the broad-spectrum COVID-19 vaccine

Appl Microbiol Biotechnol. 2024 Oct 16;108(1):486. doi: 10.1007/s00253-024-13331-y.

Abstract

Our previous study has found that monoclonal antibodies targeting a conserved epitope peptide spanning from residues 1144 to 1156 of SARS-CoV-2 spike (S) protein, namely S(1144-1156), can broadly neutralize all of the prevalent SARS-CoV-2 strains, including the wild type, Alpha, Epsilon, Delta, and Gamma variants. In the study, S(1144-1156) was conjugated with bovine serum albumin (BSA) and formulated with Montanide ISA 51 adjuvant for inoculation in BALB/c mice to study its potential as a vaccine candidate. Results showed that the titers of S protein-specific IgGs and the neutralizing antibodies in mouse sera against various SARS-CoV-2 variants, including the Omicron sublineages, were largely induced along with three doses of immunization. The significant release of IFN-γ and IL-2 was also observed by ELISpot assays through stimulating vaccinated mouse splenocytes with the S(1144-1156) peptide. Furthermore, the vaccination of the S(1143-1157)- and S(1142-1158)-EGFP fusion proteins can elicit more SARS-CoV-2 neutralizing antibodies in mouse sera than the S(1144-1156)-EGFP fusion protein. Interestingly, the antisera collected from mice inoculated with the S(1144-1156) peptide vaccine exhibited better efficacy for neutralizing Omicron BA.2.86 and JN.1 subvariants than Omicron BA.1, BA.2, and XBB subvariants. Since the amino acid sequences of the S(1144-1156) are highly conserved among various SARS-CoV-2 variants, the immunogen containing the S(1144-1156) core epitope can be designed as a broadly effective COVID-19 vaccine. KEY POINTS: • Inoculation of mice with the S(1144-1156) peptide vaccine can induce bnAbs against various SARS-CoV-2 variants. • The S(1144-1156) peptide stimulated significant release of IFN-γ and IL-2 in vaccinated mouse splenocytes. • The S(1143-1157) and S(1142-1158) peptide vaccines can elicit more SARS-CoV-2 nAbs in mice.

Keywords: Broadly neutralizing antibody (bnAb); Cellular immunity; Epitope peptide; Humoral immunity; SARS-CoV-2; Spike protein.

MeSH terms

  • Animals
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Epitopes* / immunology
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred BALB C*
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / immunology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology

Substances

  • Spike Glycoprotein, Coronavirus
  • COVID-19 Vaccines
  • Antibodies, Neutralizing
  • spike protein, SARS-CoV-2
  • Antibodies, Viral
  • Epitopes
  • Immunoglobulin G
  • Peptides
  • Interferon-gamma

Supplementary concepts

  • SARS-CoV-2 variants