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

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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.
OriginalsprogEngelsk
Artikelnummer5624
TidsskriftNature Communications
Vol/bind14
Udgave nummer1
Antal sider15
ISSN2041-1723
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The authors would like to thank Mads Engelhardt Knudsen, Sif Kaas Nielsen, Bettina Eide Holm, Victoria Marie Linderod Larsen and Emilie Caroline Skuladottir Bøgestad from the Laboratory of Molecular Medicine at Rigshospitalet; Betina Poulsen from the The Blood Bank, Department of Clinical Immunology, Rigshospitalet; Lisbeth Andreasen, Annie Mørk, Fie Andreasen, Ann Kristine Thorsteinsson, Tung Thanh Phan, and Ida Stenroos-Dam from the Department of Clinical Biochemistry at Rigshospitalet, for their excellent technical assistance in processing and analyzing the samples. We would also like to thank Alexandra Rosengaard Röthlin Eriksen from the Department of Emergency Medicine, Herlev and Gentofte Hospital, for her logistics and sample collection assistance. Bio- and Genome Bank Denmark is acknowledged for handling and storage of biological material. This work was financially supported by grants from the Carlsberg Foundation (CF20-476 0045), granted to P.G.; the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201), granted to P.G.; and the Svend Andersen Research Foundation (SARF2021), granted to P.G.

Funding Information:
The authors would like to thank Mads Engelhardt Knudsen, Sif Kaas Nielsen, Bettina Eide Holm, Victoria Marie Linderod Larsen and Emilie Caroline Skuladottir Bøgestad from the Laboratory of Molecular Medicine at Rigshospitalet; Betina Poulsen from the The Blood Bank, Department of Clinical Immunology, Rigshospitalet; Lisbeth Andreasen, Annie Mørk, Fie Andreasen, Ann Kristine Thorsteinsson, Tung Thanh Phan, and Ida Stenroos-Dam from the Department of Clinical Biochemistry at Rigshospitalet, for their excellent technical assistance in processing and analyzing the samples. We would also like to thank Alexandra Rosengaard Röthlin Eriksen from the Department of Emergency Medicine, Herlev and Gentofte Hospital, for her logistics and sample collection assistance. Bio- and Genome Bank Denmark is acknowledged for handling and storage of biological material. This work was financially supported by grants from the Carlsberg Foundation (CF20-476 0045), granted to P.G.; the Novo Nordisk Foundation (NFF205A0063505 and NNF20SA0064201), granted to P.G.; and the Svend Andersen Research Foundation (SARF2021), granted to P.G.

Publisher Copyright:
© 2023, Springer Nature Limited.

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