Effect of SARS-CoV-2 specific cellular and humoral immunity after bivalent BA.4/5 COVID-19 vaccination on subsequent breakthrough infections in previously infected and non-infected individuals
URSCHEL R. 1, BRONDER S. 1, KLEMIS V. 1, MARX S. 1, HIELSCHER F. 1, ABU-OMAR A. 1, GUCKELMUS C. 1, SCHNEITLER S. 2, BAUM C. 3, BECKER S. 2, GÄRTNER B. 2, SESTER U. 4, WIDERA M. 5, SCHMIDT T. 1, SESTER M. 1
1 Department of Transplant and Infection Immunology, Saarland University, Homburg, Germany; 2 Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany; 3 Occupational Health Care Center, Saarland University, Homburg, Germany; 4 Department of Nephrology, SHG-Klinikum Völklingen, Völklingen, Germany; 5 Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
Objectives: Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and how bivalent vaccine-induced antibodies and T-cells protect from subsequent infection in the Omicron era.
Methods: 127 immunocompetent participants were recruited, of whom 64 had a history of SARS-CoV-2 infection. Blood samples were analysed before and 2 weeks after vaccination with the bivalent vaccine. SARS-CoV-2-specific T-cells towards SARS-CoV-2 spike protein from the parental strain and variants BA.1, BA.2 and BA.4/5, including expression of cytokines IFNγ, IL-2 and TNFα as well as CTLA-4 were determined using flow cytometry. Spike-specific IgG-antibodies were quantified by ELISA and neutralising capacity by a microneutralisation assay. All individuals were followed-up for development of breakthrough infections.
Results: Both groups showed a significant vaccine-induced increase of anti-spike IgG-levels as well as neutralising antibodies and spike-specific CD4 and CD8 T-cell levels (p<0.0001, respectively). After vaccination similar levels of spike-specific T-cells were found towards the parental strain and different Omicron variants. Individuals with previous infection showed higher levels of anti-spike IgG before and after vaccination compared to non-infected individuals (p<0.0001, respectively). In contrast, no significant difference in spike-specific T-cell levels after vaccination was found between the groups. Cytokine expression was similar for the different variant specific T-cells in both the non-infected and infected with predominantly polyfunctional characteristics. No differences in CTLA-4 expression were observed between the groups. Follow-up analysis showed significantly more frequent vaccine breakthrough infections in previously non-infected participants (p=0.046), who had significantly lower levels of vaccine-induced neutralising titers and specific CD4 T-cells than individuals without breakthrough infections.
Conclusions: Immune responses after bivalent vaccination differ depending on prior history of infection, and the magnitude of vaccine-induced neutralising activity and specific CD4 T-cells may serve as a correlate for protection in previously non-infected individuals.