Durable spike-specific T cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination.

Several COVID-19 vaccines are approved to prevent severe disease outcome after SARS-CoV-2 infection. Whereas induction and functionality of antiviral antibody response are largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we report on T cell immunity 4 weeks and 6 months after different vaccination regimens and 4 weeks after an additional booster vaccination in comparison with SARS-CoV-2 T cell responses in convalescents and prepandemic donors using interferon-gamma ELISpot assays and flow cytometry. Increased T cell responses and cross-recognition of B.1.1.529 Omicron variant-specific mutations were observed ex vivo in mRNA- and heterologous-vaccinated donors compared with vector-vaccinated donors. Nevertheless, potent expandability of T cells targeting the spike protein was observed for all vaccination regimens, with frequency, diversity, and the ability to produce several cytokines of vaccine-induced T cell responses comparable with those in convalescent donors. T cell responses for all vaccinated donors significantly exceeded preexisting cross-reactive T cell responses in prepandemic donors. Booster vaccination led to a significant increase in anti-spike IgG responses, which showed a marked decline 6 months after complete vaccination. In contrast, T cell responses remained stable over time after complete vaccination with no significant effect of booster vaccination on T cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations. This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4 and CD8 T cell immunity to SARS-CoV-2.