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Triple COVID-19 vaccination induces humoral and cellular immunity to SARS-CoV-2 with cross-recognition of the Omicron variant and IgA secretion

Ruhl, L.; Kuehne, J. F.; Beushausen, K.; Keil, J.; Christoph, S.; Sauer, J.; Falk, C. S.

2022-09-22 immunology
10.1101/2022.09.22.508999 bioRxiv
Show abstract

COVID-19 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 COVID-19 vaccinations. 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.

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