A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity

Nature. 2022 Jan;601(7894):617-622. doi: 10.1038/s41586-021-04232-5. Epub 2021 Nov 23.


T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18-80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / adverse effects
  • COVID-19 Vaccines / immunology*
  • Clinical Trials, Phase II as Topic
  • Female
  • Granuloma / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology*
  • Young Adult


  • COVID-19 Vaccines
  • Vaccines, Subunit
  • Interferon-gamma

Supplementary concepts

  • SARS-CoV-2 variants