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

Abstract

AbstractBackgroundT 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.MethodWe 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.FindingsCoVac-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).InterpretationTogether, 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).FundingThis trial is funded by the Ministry of Science, Research and the Arts Baden- Württemberg., GermanyRESEARCH IN CONTEXTEvidence before this studyT cells have an important role for COVID-19 outcome and maintenance of SARS-CoV-2 immunity, even in the absence of humoral immune responses. Thus, the induction of SARS-CoV-2 T cell immunity is a central goal for vaccine development and of particular importance for patients with congenital or acquired B cell deficiencies. We developed the peptide-based T-cell activator CoVac-1, composed of SARS-CoV-2 T-cell epitopes derived from various viral proteins. In a Phase I trial in healthy adults, CoVac-1 induced profound T-cell immunity after single dose administration in 100% of participants. The multifunctional Th1CD4+and CD8+T-cell response induced by CoVac-1 surpassed those occurring after naturally SARS-CoV-2 infection as well as after vaccination with approved vaccines.Added value of this studyHere we present the final data of our Phase I trial, evaluation of safety and immunogenicity of CoVac-1 until 12 months after administration. CoVac-1 is well tolerated without long-term immune-related side effects and induces long-lasting and broad anti-viral T cell responses in all study participants, which associate with low-infection rate in the study population.Implications of all the available evidenceVarious vaccines have been approved to prevent severe COVID-19, primarily designed to induce a spike-specific humoral immune response. CoVac-1 is the first T-cell activator for induction of broad and sustained SARS-CoV-2 T-cell immunity. Accordingly, CoVac-1 may well serve as a (complementary) vaccine to induce T cell immunity, particularly in elderly and immunocompromised individuals with impaired ability to mount sufficient immune responses after SARS-CoV-2 vaccination with currently approved vaccines.