TY - JOUR

T1 - Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk

AU - Pérez-Alós, Laura

AU - Hansen, Cecilie Bo

AU - Almagro Armenteros, Jose Juan

AU - Madsen, Johannes Roth

AU - Heftdal, Line Dam

AU - Hasselbalch, Rasmus Bo

AU - Pries-Heje, Mia Marie

AU - Bayarri-Olmos, Rafael

AU - Jarlhelt, Ida

AU - Hamm, Sebastian Rask

AU - Møller, Dina Leth

AU - Sørensen, Erik

AU - Ostrowski, Sisse Rye

AU - Frikke-Schmidt, Ruth

AU - Hilsted, Linda Maria

AU - Bundgaard, Henning

AU - Nielsen, Susanne Dam

AU - Iversen, Kasper Karmark

AU - Garred, Peter

N1 - Publisher Copyright: © 2023, Springer Nature Limited.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-023-41342-2

DO - 10.1038/s41467-023-41342-2

M3 - Journal article

C2 - 37699890

AN - SCOPUS:85170696898

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5624

ER -