%0 Journal Article
%T 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.
%A Almanzar G
%A Koosha K
%A Vogt T
%A Stein A
%A Ziegler L
%A Asam C
%A Weps M
%A Schwägerl V
%A Richter L
%A Hepp N
%A Fuchs A
%A Wagenhäuser I
%A Reusch J
%A Krone M
%A Geldmacher C
%A Protzer U
%A Steininger P
%A Überla K
%A Wagner R
%A Liese J
%A Prelog M
%J J Med Virol
%V 96
%N 6
%D 2024 Jun
%M 38899449
%F 20.693
%R 10.1002/jmv.29739
%X 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.