Precise Epitope Organization with Self-adjuvant Framework Nucleic Acid for Efficient COVID-19 Peptide Vaccine Construction

Angew Chem Int Ed Engl. 2023 May 15;62(21):e202301147. doi: 10.1002/anie.202301147. Epub 2023 Apr 17.

Abstract

Peptide vaccines have advantages in easy fabrication and high safety, but their effectiveness is hampered by the poor immunogenicity of the epitopes themselves. Herein, we constructed a series of framework nucleic acids (FNAs) with regulated rigidity and size to precisely organize epitopes in order to reveal the influence of epitope spacing and carrier rigidity on the efficiency of peptide vaccines. We found that assembling epitopes on rigid tetrahedral FNAs (tFNAs) with the appropriate size could efficiently enhance their immunogenicity. Further, by integrating epitopes from SARS-CoV-2 on preferred tFNAs, we constructed a COVID-19 peptide vaccine which could induce high titers of IgG against the receptor binding domain (RBD) of SARS-CoV-2 spike protein and increase the ratio of memory B and T cells in mice. Considering the good biocompatibility of tFNAs, our research provides a new idea for developing efficient peptide vaccines against viruses and possibly other diseases.

Keywords: COVID-19; Epitope Organization; Framework Nucleic Acids; Peptide Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 Vaccines*
  • COVID-19* / prevention & control
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / metabolism
  • Humans
  • Mice
  • Peptides
  • SARS-CoV-2 / metabolism
  • Vaccines, Subunit

Substances

  • COVID-19 Vaccines
  • spike protein, SARS-CoV-2
  • Epitopes, T-Lymphocyte
  • Epitopes, B-Lymphocyte
  • Peptides
  • Vaccines, Subunit