Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults (preprint)

Background: T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants. Method: We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human clinical trial and observed a favorable safety profile and induction of poly-specific T cell responses until month 3. Here, we report on long-term safety and efficacy data of CoVac-1 in healthy adults until month 12. Findings: CoVac-1 is well tolerated without long-term immune-related side effects and induces long-lasting anti-viral T cell responses in 100% of study participants. Potent expandability of CD4+ and CD8+ T cells targeting multiple different CoVac-1 T cell epitopes was observed 6 and 12 months after one single dose of CoVac-1. T cell responses were associated with the severity and the number of local adverse events at injection site. Beyond induction of T cell immunity, 89% of study participants developed CoVac-1-specific IgG antibody titers which associated with the intensity of the T cell response, indicating that CoVac-1-specific CD4+ T cells support the induction of B cell responses. Vaccination with approved COVID-19 vaccines boosted CoVac-1-specific T cell responses. Overall, a low SARS-CoV-2 infection rate was observed in the study population (8.3% of participants until month 12). Interpretation: Together, a single application of CoVac-1 elicits long-lived and broad SARS-CoV-2-specific T cell immunity, which further supports the current evaluation of our T cell activator in patients with congenital or acquired B cell defects (NCT04954469). Funding: This trial is funded by the Ministry of Science, Research and the Arts Baden-Wuerttemberg., Germany

Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency (preprint)

T-cell immunity is central for the control of COVID-19, in particular in patients incapable to mount a humoral immune response. We previously reported on the favorable safety profile and efficacy in terms of induction of SARS-CoV-2-specific T-cell responses by CoVac-1, a peptide-based T-cell activator, composed of SARS-CoV-2 T-cell epitopes derived from various viral proteins, combined with the toll-like receptor 1/2 agonist XS151. We conducted a Phase I/II open-label trial recruiting 54 patients with congenital or acquired B-cell deficiency who received one single subcutaneous dose of CoVac-1. Immunogenicity until day 28 in terms of CoVac-1-induced T-cell responses was the primary endpoint; safety until day 56 was assessed as secondary endpoint. Neither serious nor grade 4 CoVac-1-related adverse events were observed. The expected local granuloma formation was observed in 94% of study subjects, whereas systemic reactogenicity was mostly mild or absent. SARS-CoV-2-specific Tcell responses were induced in 86% of the patients and directed to multiple CoVac-1 peptides, not affected by any current Omicron variants and mediated by multifunctional T-helper 1 CD4+ T cells. CoVac-1-induced T-cell responses exceeded spike-specific T-cell responses after vaccination with mRNA vaccines in B-cell deficient patients and also that of immunocompetent COVID-19 convalescents with and without seroconversion. CoVac-1 induces broad and potent T-cell responses in patients with Bcell/antibody deficiency independently of current variants of concern, with a favorable safety profile. Our data warrant advancement to a pivotal Phase II/III safety and efficacy evaluation.

Phase I Trial of a Multi-Peptide COVID-19 Vaccine for the Induction of SARS-CoV-2 T-Cell Immunity (preprint)

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 proteins, combined with the toll-like receptor 1/2 agonist XS15 emulsified in Montanide TM ISA51 VG, aiming to induce superior SARS-CoV-2 T-cell immunity to combat COVID-19. We conducted a Phase I open-label trial, including 36 participants aged 18 to 80 years, who received one single subcutaneous CoVAC-1 vaccination. The primary endpoint was safety analyzed until day 56. Immunogenicity in terms of CoVac-1-induced T-cell response was analyzed as main secondary endpoint until day 28. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study subjects, while 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 interferon-γ T-cell responses by far surpassed those detected in COVID-19 convalescents and were unaffected by current SARS-CoV-2 variants of concern (VOC). Together, CoVac-1 showed a favorable safety profile and induced broad, potent, and VOC-independent T-cell responses, supporting the presently ongoing evaluation in a Phase II trial for patients with B-cell/antibody deficiency. Funded by the Ministry of Science, Research and the Arts Baden-Württemberg, Germany; ClinicalTrials.gov number, NCT04546841.