Hybrid immunity by two COVID‐19 mRNA vaccinations and one breakthrough infection provides a robust and balanced cellular immune response as basic immunity against severe acute respiratory syndrome coronavirus 2

Author:

Almanzar Giovanni1,Koosha Kimia1,Vogt Tim1,Stein Astrid1,Ziegler Lars1,Asam Claudia2,Weps Manuela2,Schwägerl Valeria1,Richter Lorena1,Hepp Nicola1,Fuchs Andre3,Wagenhäuser Isabell4,Reusch Julia4,Krone Manuel4ORCID,Geldmacher Christof56,Protzer Ulrike78,Steininger Philipp9,Überla Klaus9,Wagner Ralf2,Liese Johannes1,Prelog Martina1

Affiliation:

1. Department of Pediatrics, Pediatric Rheumatology/Special Immunology University Hospital Würzburg Würzburg Germany

2. Institute of Clinical Microbiology and Hygiene University Hospital Regensburg Regensburg Germany

3. Internal Medicine III—Gastroenterology and Infectious Diseases University Hospital of Augsburg Augsburg Germany

4. Institute for Hygiene and Microbiology Julius‐Maximilian‐Universität Würzburg Würzburg Germany

5. Division of Infectious Diseases and Tropical Medicine University Hospital, Ludwig‐Maximilians‐Universität (LMU) Munich Munich Germany

6. German Centre for Infection Research (DZIF) Partner Site Munich Munich Germany

7. School of Medicine, Institute of Virology Technical University of Munich Munich Germany

8. German Center for Infection Research Institute of Virology, Helmholtz Munich, Munich Partner Site Munich Germany

9. Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany

Abstract

AbstractThis longitudinal prospective controlled multicenter study aimed to monitor immunity generated by three exposures caused by breakthrough infections (BTI) after COVID‐19‐vaccination considering pre‐existing cell‐mediated immunity to common‐corona‐viruses (CoV) which may impact cellular reactivity against SARS‐CoV‐2. Anti‐SARS‐CoV‐2‐spike‐IgG antibodies (anti‐S‐IgG) and cellular reactivity against Spike‐(S)‐ and nucleocapsid‐(N)‐proteins were determined in fully‐vaccinated (F) individuals who either experienced BTI (F+BTI) or had booster vaccination (F+Booster) compared to partially vaccinated (P+BTI) and unvaccinated (U) from 1 to 24 weeks post PCR‐confirmed infection. High avidity anti‐S‐IgG were found in F+BTI compared to U, the latter exhibiting increased long‐lasting pro‐inflammatory cytokines to S‐stimulation. CoV was associated with higher cellular reactivity in U, whereas no association was seen in F. The study illustrates the induction of significant S‐specific cellular responses in F+BTI building‐up basic immunity by three exposures. Only U seem to benefit from pre‐existing CoV immunity but demonstrated inflammatory immune responses compared to F+BTI who immunologically benefit from enhanced humoral and cellular immunity after BTI. This study demonstrates that individuals with hybrid immunity from COVID‐19‐vaccination and BTI acquire a stable humoral and cellular immune response that is maintained for at least 6 months. Our findings corroborate recommendations by health authorities to build on basic immunity by three S‐protein exposures.

Publisher

Wiley

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