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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

See all articles by Louisa Ruhl

Louisa Ruhl

Hannover Medical School - Institute of Immunology

Jenny F. Kuehne

Hannover Medical School - Institute of Immunology

Kerstin Beushausen

Hannover Medical School - Institute of Immunology

Jana Keil

Hannover Medical School - Institute of Immunology

Stella Christoph

Hannover Medical School - Institute of Immunology

Jasper Sauer

Hannover Medical School - Institute of Immunology

Christine S. Falk

Hannover Medical School - Institute of Immunology

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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

Suggested Citation

Ruhl, Louisa and Kuehne, Jenny F. and Beushausen, Kerstin and Keil, Jana and Christoph, Stella and Sauer, Jasper and Falk, Christine S., Third SARS-CoV-2 Vaccination and Breakthrough Infections Enhance Humoral and Cellular Immunity Against Variants of Concern. Available at SSRN: https://ssrn.com/abstract=4254225 or http://dx.doi.org/10.2139/ssrn.4254225
This version of the paper has not been formally peer reviewed.

Louisa Ruhl

Hannover Medical School - Institute of Immunology ( email )

Jenny F. Kuehne

Hannover Medical School - Institute of Immunology ( email )

Kerstin Beushausen

Hannover Medical School - Institute of Immunology ( email )

Jana Keil

Hannover Medical School - Institute of Immunology ( email )

Stella Christoph

Hannover Medical School - Institute of Immunology ( email )

Jasper Sauer

Hannover Medical School - Institute of Immunology ( email )

Christine S. Falk (Contact Author)

Hannover Medical School - Institute of Immunology ( email )

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