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J Med Virol . Hybrid immunity by two COVID-19 mRNA vaccinations and one breakthrough infection provides a robust and balanced cellular immune respo

tetano

Editor, Senior Moderator
J Med Virol


. 2024 Jun;96(6):e29739.
doi: 10.1002/jmv.29739. 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

Giovanni Almanzar[SUP] 1 [/SUP], Kimia Koosha[SUP] 1 [/SUP], Tim Vogt[SUP] 1 [/SUP], Astrid Stein[SUP] 1 [/SUP], Lars Ziegler[SUP] 1 [/SUP], Claudia Asam[SUP] 2 [/SUP], Manuela Weps[SUP] 2 [/SUP], Valeria Schwägerl[SUP] 1 [/SUP], Lorena Richter[SUP] 1 [/SUP], Nicola Hepp[SUP] 1 [/SUP], Andre Fuchs[SUP] 3 [/SUP], Isabell Wagenhäuser[SUP] 4 [/SUP], Julia Reusch[SUP] 4 [/SUP], Manuel Krone[SUP] 4 [/SUP], Christof Geldmacher[SUP] 5 6 [/SUP], Ulrike Protzer[SUP] 7 8 [/SUP], Philipp Steininger[SUP] 9 [/SUP], Klaus Überla[SUP] 9 [/SUP], Ralf Wagner[SUP] 2 [/SUP], Johannes Liese[SUP] 1 [/SUP], Martina Prelog[SUP] 1 [/SUP]



Affiliations
Abstract

This 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.

Keywords: COVID‐19; SARS‐CoV‐2; breakthrough infection; common corona viruses; hybrid immunity; mRNA vaccination.

 
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