ABSTRACT
Heterologous priming with the ChAdOx1-nCoV-19 vector-vaccine followed by boosting with an mRNA-vaccine is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. Here we show that the heterologous regimen induced spike-specific IgG, neutralizing antibodies, and spike-specific CD4 T-cells, which were significantly more pronounced than after homologous vector boost, and higher or comparable in magnitude to the homologous mRNA regimens. Moreover, spike-specific CD8 T-cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Cytokine expression profiling showed a predominance of polyfunctional T-cells expressing IFN{gamma}, TNF and IL-2 with subtle differences between regimens. Both recipients of the homologous vector-regimen and the heterologous vector/mRNA-combination were most affected by the priming vector-vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA-boosting. Taken together, heterologous vector-mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profile. This knowledge will have implications for future vaccine strategies.
ABSTRACT
Knowledge on the vaccine-induced cellular and humoral immunity and on immunogenicity of vector-based and mRNA vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2 specific T-cells and antibodies were analyzed in 40 transplant recipients and 70 age-matched controls after the first dose of vector-based or mRNA vaccines. Plasmablasts and SARS-CoV-2 specific CD4 and CD8 T-cells were quantified using flow-cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. SARS-CoV-2 specific antibodies and T-cells were induced in both groups with significantly lower levels in patients. While antibodies were detected in 80% of controls and 5.3% of patients, specific CD4 and/or CD8 T-cells were more frequently found in both controls (84.3%) and patients (23.7%). The two vaccine types showed notable differences, as IgG and neutralizing activity were more pronounced after mRNA vaccination (p<0.0001 each), whereas CD4 and CD8 T-cell levels were higher after vector vaccination (p=0.009; p<0.0001). Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2 specific IgG- and CD4 T-cell levels. In conclusion, assessment of antibodies is not sufficient to identify COVID-19-vaccine responders. Together with differences in immunogenicity among vaccines, this necessitates combined analysis of humoral and cellular immunity to reliably assess responders among immunocompetent and immunocompromised individuals.
ABSTRACT
Patients infected with SARS-CoV-2 differ in the severity of disease. In this study, SARS-CoV-2 specific T-cells and antibodies were characterized in patients with different COVID-19 related disease severity. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals. SARS-CoV-2 specific CD4 T-cells dominated over CD8 T-cells and closely correlated with the number of plasmablasts and SARS-CoV-2 specific IgA- and IgG-levels. Unlike in convalescents, SARS-CoV-2 specific T-cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 and CD8 T-cells in general. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered phenotype may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.
