Third SARS-CoV-2 Vaccination and Breakthrough Infections Enhance Humoral and Cellular Immunity Against Variants of Concern
39 Pages Posted: 3 Nov 2022 Publication Status: Review Complete
More...Abstract
SARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections. All individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron independently from age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed a SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to appearance of new variant-specific antibodies. In conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.
Funding Information: This project was supported by the German Research Foundation DFG FA-483/1-1, the German Center for Infection Research DZIF TTU-IICH 07_913, the Lower Saxony Ministry of Research and Culture (ImProVIT) and the COFONI fast track project 8FT21.
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: The study was approved by the Hannover Medical School Ethics Committee. All patients or participants provided written informed consent before participation in the study (9001 BO K, 968-2011).
Keywords: SARS-CoV-2 vaccination, COVID-19, breakthrough infection, Omicron, IgA, antibody, T cells, variants of concern, elderly individuals
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