Viral T-cell epitopes - Identification, characterization and clinical application.

T-cell immunity, mediated by CD4+ and CD8+ T cells, represents a cornerstone in the control of viral infections. Virus-derived T-cell epitopes are represented by human leukocyte antigen (HLA)-presented viral peptides on the surface of virus-infected cells. They are the prerequisite for the recognition of infected cells by T cells. Knowledge of viral T-cell epitopes provides on the one hand a diagnostic tool to decipher protective T-cell immune responses in the human population and on the other hand various prophylactic and therapeutic options including vaccination approaches and the transfer of virus-specific T cells. Such approaches have already been proven to be effective against various viral infections, particularly in immunocompromised patients lacking sufficient humoral, antibody-based immune response. This review provides an overview on the state of the art as well as current studies regarding the identification and characterization of viral T-cell epitopes and approaches of clinical application. In the first chapter in silico prediction tools and direct, mass spectrometry-based identification of viral T-cell epitopes is compared. The second chapter provides an overview of commonly used assays for further characterization of T-cell responses and phenotypes. The final chapter presents an overview of clinical application of viral T-cell epitopes with a focus on human immunodeficiency virus (HIV), human cytomegalovirus (HCMV) and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), being representatives of relevant viruses.

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 following SARS-CoV-2 infection. Whereas the induction and functionality of anti-viral antibody response is largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we reported on T-cell immunity four weeks and six months after different vaccination regimens and four weeks after an additional booster vaccination, in comparison to 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 to 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 to 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 of anti-spike IgG responses, which showed a marked decline 6 month after complete vaccination. In contrast, T-cell responses remained stable over time following 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.