Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

Laura Pérez-Alós (), Cecilie Bo Hansen, Jose Juan Almagro Armenteros, Johannes Roth Madsen, Line Dam Heftdal, Rasmus Bo Hasselbalch, Mia Marie Pries-Heje, Rafael Bayarri-Olmos, Ida Jarlhelt, Sebastian Rask Hamm, Dina Leth Møller, Erik Sørensen, Sisse Rye Ostrowski, Ruth Frikke-Schmidt, Linda Maria Hilsted, Henning Bundgaard, Susanne Dam Nielsen, Kasper Karmark Iversen and Peter Garred ()
Additional contact information
Laura Pérez-Alós: Copenhagen University Hospital, Rigshospitalet
Cecilie Bo Hansen: Copenhagen University Hospital, Rigshospitalet
Jose Juan Almagro Armenteros: Stanford University School of Medicine
Johannes Roth Madsen: Copenhagen University Hospital, Rigshospitalet
Line Dam Heftdal: Copenhagen University Hospital, Rigshospitalet
Rasmus Bo Hasselbalch: Copenhagen University Hospital Herlev and Gentofte
Mia Marie Pries-Heje: Copenhagen University Hospital, Rigshospitalet
Rafael Bayarri-Olmos: Copenhagen University Hospital, Rigshospitalet
Ida Jarlhelt: Copenhagen University Hospital, Rigshospitalet
Sebastian Rask Hamm: Copenhagen University Hospital, Rigshospitalet
Dina Leth Møller: Copenhagen University Hospital, Rigshospitalet
Erik Sørensen: Copenhagen University Hospital, Rigshospitalet
Sisse Rye Ostrowski: Copenhagen University Hospital, Rigshospitalet
Ruth Frikke-Schmidt: University of Copenhagen
Linda Maria Hilsted: Copenhagen University Hospital, Rigshospitalet
Henning Bundgaard: Copenhagen University Hospital, Rigshospitalet
Susanne Dam Nielsen: Copenhagen University Hospital, Rigshospitalet
Kasper Karmark Iversen: Copenhagen University Hospital Herlev and Gentofte
Peter Garred: Copenhagen University Hospital, Rigshospitalet

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections.

Date: 2023
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DOI: 10.1038/s41467-023-41342-2

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