COVID-19 peptide vaccine safety and immunogenicity

Variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise around the world. The Gamma version is causing havoc in South America, while the Delta variation is responsible for the majority of new infections in the United States and Europe. These variants have demonstrated their ability to circumvent both vaccine-induced and natural immunity on numerous occasions. The increasing number of cases across Europe has led some countries to revert to costly and stringent lockdowns.

COVID-19 peptide vaccine

Researchers from University Hospital Tübingen investigated the findings of a Phase I trial for a novel vaccination against SARS-CoV-2 variants in a report published in Nature.

The research

In the first phase of the study, 12 healthy adults were chosen to receive the medication. This was increased to 24 in the second part. On day one, volunteers received one dose of the CoVac-1 vaccination and were monitored for immunogenicity and safety until days 28 and 56. There were no major side effects, and there were no grade four side effects. Mild-to-moderate incidents occurred in 18-81 percent of subjects.


A granuloma/induration formed at the injection site, as expected, and lasted the duration of the experiment. Six percent of individuals experienced a grade 3 adverse reaction, with erythema (a type of skin rash) accounting for 19% of these, and severe edema accounting for another 6%. Lymphangitis (swelling of lymph nodes) was observed by 22% of patients, while ulcerations at the vaccination site were recorded by 25%. Two of the ulcers were grade 2, however they all healed within 20 days without the need for surgery or medication. There were no reports of fever or other inflammatory side effects, and all other systemic side effects were minor. There was no evidence of SARS-CoV-2 infection in any of the participants.

The researchers used interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) tests to examine CD4+ and CD8+ T cell responses to six SARS-CoV-2 HLA-DR vaccine T-cell epitopes, as well as HLA class I-binding peptides, to determine the vaccine’s immunogenicity. They looked at T cell responses at baseline, 7, 14, 28, and 56 days after immunization, as well as three months afterwards. At the start of the study, all subjects tested negative for SARS-CoV-2 T cell response.

All participants had a 100/200 fold increase in responsiveness from baseline by day 28. The majority of these reactions targeted CoVac-1 peptides, with the ORF-8 generated from SARS-CoV-2 being the most targeted, followed by P5-mem and P4-env, but all peptides were targeted. P2 nuc had the lowest response rate, at only 58 percent. All participants’ responses lasted until month 3, however the IFN-gamma T cell response diminished over time.

The intensity of these responses was nevertheless significantly higher than that of people who had previously been infected with coronavirus disease 2019 (COVID-19), with a rise of up to 39-fold. The vaccine-induced T cells were likewise highly reactive, recognizing peptides at concentrations as low as 1 mg/mL. The response was very impressive in terms of intensity, outperforming spike-specific T cell responses elicited by mRNA adenoviral vector-based vaccination and classical heterologous vaccination.

The researchers then looked at how well the CoVac-1-induced immune activity responded to specific variants of concern, such as Alpha, Beta, Gamma, and Delta, which have all shown the potential to resist previously induced immunity. Any mutation related with these variants had no effect on half of the vaccination peptides.

The peptides are unaffected by any of the changes in the Delta or Gamma strains. Two of the peptides, P2 nuc and P6 ORF8, are affected by the Alpha strain, whereas P3 spi is affected by the Beta variation with two different amino acid alterations.

T-cell responses to peptide pools containing these altered peptides, on the other hand, were still detectable in every individual, even against the peptides that were impacted. The T-cell response was lowered in intensity, but the vaccine should still provide adequate protection.


This Phase I experiment, according to the scientists, reveals that this vaccine candidate is relatively safe and elicits robust immune responses following a single shot.

While there were some side effects, none of them were life-threatening or very harmful. A major advantage of the vaccine is the diversity of the generated T-cell response. Anti-spike IgGs were even found in some people, implying that the T-cell response could excite B cells and increase cross-reactive SARS-CoV-2 antibodies.

As new variants of concern emerge, this vaccine could prove invaluable in protecting the most vulnerable against SARS-CoV-2 and limiting the spread of variants that have shown the propensity to induce breakthrough infections even in people who have been fully vaccinated.