Immune Response in Moderate to Critical Breakthrough COVID-19 Infection After mRNA Vaccination

Frontiers in Immunology

Nina Babel¹  Toralf Roch¹  Constantin J. Thieme¹  Sarah Skrzypczyk²  Moritz Anft²  Krystallenia Paniskaki²  Ulrik Stervbo²  Margarethe J. Konik³  Oliver Witzke³  Hana Rohn³  Sebastian Dolff³  Corinna Marheinecke⁴  Stephanie Pfaender⁴  Toni L. Meister⁴  Christine Queren⁵  Lutz Fricke⁵  Ulf Dittmer⁶  Olympia Anastasiou⁶  Timm H. Westhoff⁷  Felix S. Seibert⁷  Bodo Holzer⁷ 

[1] Berlin Institute of Health at Charité – University Clinic Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany;Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany;Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany;Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany;Dialysis Center Dialyse Bochum, Bochum, Germany;Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany;Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany;

关键词: SARS-CoV-2;    vaccine;    mRNA;    breakthrough infection;    T cells;    neutralizing antibodies;   

DOI  :  10.3389/fimmu.2022.816220

来源: DOAJ

【 摘 要 】

SARS-CoV-2 variants of concern (VOCs) can trigger severe endemic waves and vaccine breakthrough infections (VBI). We analyzed the cellular and humoral immune response in 8 patients infected with the alpha variant, resulting in moderate to fatal COVID-19 disease manifestation, after double mRNA-based anti-SARS-CoV-2 vaccination. In contrast to the uninfected vaccinated control cohort, the diseased individuals had no detectable high-avidity spike (S)-reactive CD4+ and CD8+ T cells against the alpha variant and wild type (WT) at disease onset, whereas a robust CD4+ T-cell response against the N- and M-proteins was generated. Furthermore, a delayed alpha S-reactive high-avidity CD4+ T-cell response was mounted during disease progression. Compared to the vaccinated control donors, these patients also had lower neutralizing antibody titers against the alpha variant at disease onset. The delayed development of alpha S-specific cellular and humoral immunity upon VBI indicates reduced immunogenicity against the S-protein of the alpha VOC, while there was a higher and earlier N- and M-reactive T-cell response. Our findings do not undermine the current vaccination strategies but underline a potential need for the inclusion of VBI patients in alternative vaccination strategies and additional antigenic targets in next-generation SARS-CoV-2 vaccines.

【 授权许可】

Unknown