Vaccine-induced CD8 T-cells maintain enhanced cytotoxicity and proliferation in SARS-CoV-2 breakthrough infections in hematological cancer patients 4221

Abstract Description Despite the considerable impact of COVID-19 vaccination on protection from disease severity and mortality, SARS-CoV-2 breakthrough infections are substantially high in patients with hematological cancers. This could be attributed to the impaired antibody response in this group of patients. Thus, we analyzed the impact of vaccine-induced T-cells in CLL and MDS patients, immunized up to five times, by longitudinally profiling antigen-specific CD8 T-cells up to 2 years post-vaccination. Furthermore, we employed a single-cell analysis pipeline integrating antigen-specific pMHC multimers, single-cell RNA sequencing (ScRNA-seq), single-cell T-cell receptor sequencing (scTCRseq), and CITEseq to comprehensively evaluate antigen-specific CD8 T-cells for their phenotypes induced by vaccination and infection, TCR diversity, and the evolution of pre-existing T-cells during breakthrough infections. we found that repetitive vaccination boosted vaccine-induced immunodominant T-cell responses without impacting the functional phenotype of such T-cells. In breakthrough infections, the highly cytotoxic phenotype (GZMB+ cells) was predominantly associated with the SARS-CoV-2 vaccine-induced immunodominant antigens and the pre-existing vaccine-induced T-cell showed the increased expression of genes associated with T-cell cytotoxicity. Our data highlight the importance of COVID-19 vaccine-induced T-cells in patients with hematological cancers. Funding Sources Danish Cancer Society R306-A18139 Topic Categories Viral Immunology (VIR)