Vector-based SARS-CoV-2 vaccination is associated with improved T-cell responses in hematological neoplasia

Abstract

In order to elucidate mechanisms for SARS-CoV-2 vaccination success in hematological neoplasia, we herein provide a comprehensive characterization of the spike-specific T-cell and serological immunity induced in 130 patients in comparison to 91 healthy controls. We studied 121 distinct T-cell subpopulations and the vaccination schemes as putative response predictors. In patients with lymphoid malignancies an insufficient IgG response was accompanied by a normal CD4 ⁺ T-cell function. Compared to controls, a spike-specific CD4 ⁺ response was detectable in fewer patients with myeloid neoplasia whereas the seroconversion rate was normal. In-depth immunophenotyping demonstrated in particular, that CD4 ⁺ T-cells and naïve CD4 ⁺ T-cells were reduced in both patient cohorts without differences between the groups. Vaccination-induced CD4 ⁺ responses were associated to CD8 ⁺ and IgG responses. Vector-based AZD1222 vaccine induced more frequently detectable specific CD4 ⁺ responses in study participants across all cohorts (27/28, 96%), whereas fully mRNA based vaccination schemes resulted in measurable CD4 ⁺ cells in 102/168 participants only (61%, p<0.0001). A similar benefit of vector-based vaccination was observed for the induction of spike-specific CD8 ⁺ T-cells. Multivariable models confirmed vaccination schemes that incorporated at least one vector-based vaccination as key feature to mount both a spike-specific CD4 ⁺ (odds ratio 10.67) and CD8 ⁺ response (odds ratio 6.56). Multivariable analyses identified a specific CD4 ⁺ response, but not the vector-based immunization as beneficial for a strong specific IgG titer. Our study reveals factors associated with a T-cell response in patients with hematologic neoplasia and might pave the way towards tailored vaccination schemes for vaccinees suffering from these diseases. The study is registered at the German Clinical Trials Register (DRKS00027372).