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

TY - JOUR

T1 - Omicron variant-specific serological imprinting following BA.1 or BA.4/5 bivalent vaccination and previous SARS-CoV-2 infection

T2 - A cohort study

AU - Baerends, Eva A M

AU - Reekie, Joanne

AU - Andreasen, Signe R

AU - Stærke, Nina B

AU - Raben, Dorthe

AU - Nielsen, Henrik

AU - Petersen, Kristine T

AU - Johansen, Isik S

AU - Lindvig, Susan O

AU - Madsen, Lone W

AU - Wiese, Lothar

AU - Iversen, Mette B

AU - Benfield, Thomas

AU - Iversen, Kasper K

AU - Larsen, Fredrikke D

AU - Andersen, Sidsel D

AU - Juhl, Anna K

AU - Dietz, Lisa L

AU - Hvidt, Astrid K

AU - Ostrowski, Sisse R

AU - Krause, Tyra G

AU - Østergaard, Lars

AU - Søgaard, Ole S

AU - Lundgren, Jens

AU - Tolstrup, Martin

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

KW - antibodies

KW - bivalent vaccines

KW - booster vaccination

KW - COVID-19

KW - immunogenicity

KW - Antibodies, Neutralizing

KW - Prospective Studies

KW - SARS-CoV-2/genetics

KW - Humans

KW - Vaccination

KW - Vaccines, Combined

KW - Antibodies, Viral

KW - COVID-19 Vaccines

KW - COVID-19/prevention & control

KW - Cohort Studies

U2 - 10.1093/cid/ciad402

DO - 10.1093/cid/ciad402

M3 - Journal article

C2 - 37392436

SN - 1058-4838

VL - 77

SP - 1511

EP - 1520

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 11

ER -