SARS-CoV-2 T-cell vaccine VB10.2210 induces broad T-cell responses in a phase 1/2 open-label clinical trial.

The repeated emergence of highly transmissive SARS-CoV-2 variants requires a broadly protective vaccine. We developed a T-cell vaccine VB10.2210 that targets SARS-CoV-2 viral antigens to antigen presenting cells comprising 96 validated immunogenic T-cell epitopes covering a global HLA diversity. We report results from a first in human open-label dose-escalation phase 1/2 clinical trial evaluating safety, reactogenicity and immunogenicity of VB10.2210. The study investigated three dose levels (0.3, 1.0 and 3.0 mg), delivered intramuscularly as DNA plasmid by jet injection (NCT05069623), in 34 healthy adults previously vaccinated with mRNA SARS-CoV-2 vaccines. The safety profile was favorable with no observed dose-limiting toxicity. The 3 mg dose elicited the most potent immune response with enhanced breadth and a CD8+ dominated T cell response. T cell responses towards spike protein and de novo responses to non-spike antigens were confirmed by ELISpot. Expansion of VB10.2210 specific T-cell clones was confirmed by TCR sequencing. Further studies are needed to evaluate the clinical benefit of DNA vaccines inducing broad virus specific T-cell immunity in preventing severe COVID-19 or as treatment of patients with persistent infection.