Omicron variant-specific serological imprinting following BA.1 or BA.4/5 bivalent vaccination and previous SARS-CoV-2 infection: A cohort study

Eva A M Baerends*, Joanne Reekie, Signe R Andreasen, Nina B Stærke, Dorthe Raben, Henrik Nielsen, Kristine T Petersen, Isik S Johansen, Susan O Lindvig, Lone W Madsen, Lothar Wiese, Mette B Iversen, Thomas Benfield, Kasper K Iversen, Fredrikke D Larsen, Sidsel D Andersen, Anna K Juhl, Lisa L Dietz, Astrid K Hvidt, Sisse R OstrowskiTyra G Krause, Lars Østergaard, Ole S Søgaard, Jens Lundgren, Martin Tolstrup

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


BACKGROUND: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified.

METHODS: In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses.

RESULTS: Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05-7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09-1.57) and BA.3 (1.32, 1.09-1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76-0.98), BA.4 (0.85, 0.75-0.97), and BA.5 (0.87, 0.76-0.99) antigens in individuals with a prior infection.

CONCLUSIONS: Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants.

Sider (fra-til)1511-1520
Antal sider10
TidsskriftClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Udgave nummer11
Tidlig onlinedato1 jul. 2023
StatusUdgivet - 30 nov. 2023

Bibliografisk note

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.


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