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. Ostrowski; Tyra G. Krause; Lars Østergaard; Ole S. Søgaard; Jens Lundgren; Martin Tolstrup; the ENFORCE Study Group; Jacob Bodilsen; Henrik Nielsen; Kristine Toft Petersen; Maria Ruwald Juhl; Rikke Krog Thisted

doi:10.1093/cid/ciad402

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, the ENFORCE Study Group, Jacob Bodilsen (Member of study group), Henrik Nielsen (Member of study group), Kristine Toft Petersen (Member of study group), Maria Ruwald Juhl (Member of study group), Rikke Krog Thisted (Member of study group)

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

4 Citations (Scopus)

19 Downloads (Pure)

Abstract

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.

Original language	English
Article number	ciad402
Journal	Clinical Infectious Diseases
Volume	77
Issue number	11
Pages (from-to)	1511–1520
Number of pages	10
ISSN	1058-4838
DOIs	https://doi.org/10.1093/cid/ciad402
Publication status	Published - 1 Dec 2023

Bibliographical note

Keywords

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19/prevention & control
Cohort Studies
Humans
Prospective Studies
SARS-CoV-2/genetics
Vaccination
Vaccines, Combined
booster vaccination
immunogenicity
COVID-19
bivalent vaccines
antibodies

Access to Document

10.1093/cid/ciad402Licence: CC BY-NC-ND 4.0

Baerends et al. (2023). Omicron Variant-Specific Serological Imprinting Following BA.1 or BA.45 Bivalent Vaccination and Previous SARS-CoV-2 Infection A Cohort StudyFinal published version, 869 KBLicence: CC BY-NC-ND 4.0

AUB Link

Search for the material in Aalborg University Library's search engine

Cite this

Baerends, E. A. M., Reekie, J., Andreasen, S. R., Stærke, N. B., Raben, D., Nielsen, H., Petersen, K. T., Johansen, I. S., Lindvig, S. O., Madsen, L. W., Wiese, L., Iversen, M. B., Benfield, T., Iversen, K. K., Larsen, F. D., Andersen, S. D., Juhl, A. K., Dietz, L. L., Hvidt, A. K., ... Thisted, R. K. (2023). Omicron variant-specific serological imprinting following BA.1 or BA.4/5 bivalent vaccination and previous SARS-CoV-2 infection: A cohort study. Clinical Infectious Diseases, 77(11), 1511–1520. Article ciad402. https://doi.org/10.1093/cid/ciad402

@article{4f4e4cf62ad9448d80447c48240ebfe2,

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

abstract = "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.",

keywords = "Antibodies, Neutralizing, Antibodies, Viral, COVID-19 Vaccines, COVID-19/prevention & control, Cohort Studies, Humans, Prospective Studies, SARS-CoV-2/genetics, Vaccination, Vaccines, Combined, booster vaccination, immunogenicity, COVID-19, bivalent vaccines, antibodies",

author = "Baerends, {Eva A. M.} and Joanne Reekie and Andreasen, {Signe R.} and St{\ae}rke, {Nina B.} and Dorthe Raben and Henrik Nielsen and Petersen, {Kristine T.} and Johansen, {Isik S.} and Lindvig, {Susan O.} and Madsen, {Lone W.} and Lothar Wiese and Iversen, {Mette B.} and Thomas Benfield and Iversen, {Kasper K.} and Larsen, {Fredrikke D.} and Andersen, {Sidsel D.} and Juhl, {Anna K.} and Dietz, {Lisa L.} and Hvidt, {Astrid K.} and Ostrowski, {Sisse R.} and Krause, {Tyra G.} and Lars {\O}stergaard and S{\o}gaard, {Ole S.} and Jens Lundgren and Martin Tolstrup and {the ENFORCE Study Group} and Jacob Bodilsen and Henrik Nielsen and Petersen, {Kristine Toft} and Juhl, {Maria Ruwald} and Thisted, {Rikke Krog}",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2023",

month = dec,

day = "1",

doi = "10.1093/cid/ciad402",

language = "English",

volume = "77",

pages = "1511–1520",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "11",

}

Baerends, EAM, Reekie, J, Andreasen, SR, Stærke, NB, Raben, D, Nielsen, H , Petersen, KT, Johansen, IS, Lindvig, SO, Madsen, LW, Wiese, L, Iversen, MB, Benfield, T, Iversen, KK, Larsen, FD, Andersen, SD, Juhl, AK, Dietz, LL, Hvidt, AK, Ostrowski, SR, Krause, TG, Østergaard, L, Søgaard, OS, Lundgren, J, Tolstrup, M, the ENFORCE Study Group, Bodilsen, J , Nielsen, H , Petersen, KT , Juhl, MR & Thisted, RK 2023, 'Omicron variant-specific serological imprinting following BA.1 or BA.4/5 bivalent vaccination and previous SARS-CoV-2 infection: A cohort study', Clinical Infectious Diseases, vol. 77, no. 11, ciad402, pp. 1511–1520. https://doi.org/10.1093/cid/ciad402

Omicron variant-specific serological imprinting following BA.1 or BA.4/5 bivalent vaccination and previous SARS-CoV-2 infection: A cohort study. / Baerends, Eva A. M.; Reekie, Joanne; Andreasen, Signe R. et al.
In: Clinical Infectious Diseases, Vol. 77, No. 11, ciad402, 01.12.2023, p. 1511–1520.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

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

AU - the ENFORCE Study Group

A2 - Bodilsen, Jacob

A2 - Nielsen, Henrik

A2 - Petersen, Kristine Toft

A2 - Juhl, Maria Ruwald

A2 - Thisted, Rikke Krog

PY - 2023/12/1

Y1 - 2023/12/1

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, Neutralizing

KW - Antibodies, Viral

KW - COVID-19 Vaccines

KW - COVID-19/prevention & control

KW - Cohort Studies

KW - Humans

KW - Prospective Studies

KW - SARS-CoV-2/genetics

KW - Vaccination

KW - Vaccines, Combined

KW - booster vaccination

KW - immunogenicity

KW - COVID-19

KW - bivalent vaccines

KW - antibodies

UR - http://www.scopus.com/inward/record.url?scp=85171966020&partnerID=8YFLogxK

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

M1 - ciad402

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

AUB Link

Other files and links

Fingerprint

Cite this