lancet-header

Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.

SARS-CoV-2 Vaccine-Induced Antibodies Protect Against Omicron Breakthrough Infection

20 Pages Posted: 24 Feb 2023

See all articles by Eva Baerends

Eva Baerends

Aarhus University - Department of Infectious Diseases

Astrid Korning Hvidt

Aarhus University - Department of Infectious Diseases

Joanne Reekie

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP

Ole S. Søgaard

Aarhus University - Department of Infectious Diseases

Nina Breinholt Stærke

Aarhus University - Department of Infectious Diseases

Dorthe Raben

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP

Henrik Nielsen

Aalborg University - Department of Infectious Diseases

Kristine Toft Petersen

Aalborg University - Department of Infectious Diseases

Maria Ruwald Juhl

Aalborg University - Department of Infectious Diseases

Isik S. Johansen

Odense University Hospital - Department of Infectious Diseases

Susan Olaf Lindvig

Odense University Hospital - Department of Infectious Diseases

Lone Wulff Madsen

Odense University Hospital - Department of Infectious Diseases

Lothar Wiese

Zealand University Hospital - Department of Infectious Diseases

Lene Surland Knudsen

Zealand University Hospital - Department of Medicine

Mette Brouw Iversen

Zealand University Hospital - Department of Medicine

Thomas Benfield

University of Copenhagen - Department of Infectious Diseases

Kasper Karmark Iversen

University of Copenhagen - Department of Cardiology

Sidsel Dahl Andersen

Aarhus University - Department of Infectious Diseases

Anna Karina Juhl

Aarhus University - Department of Infectious Diseases

Lisa Loksø Dietz

Aarhus University - Department of Infectious Diseases

Signe Rode Andreasen

Aarhus University - Department of Infectious Diseases

Thea K. Fischer

University of Copenhagen - Department of Public Health

Christian Erikstrup

Aarhus University - Department of Clinical Immunology

Palle Valentiner-Branth

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Jens Lundgren

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP

Lars Jørgen Østergaard

Aarhus University - Department of Infectious Diseases

Martin Tolstrup

Aarhus University - Department of Infectious Diseases

More...

Abstract

Background: The SARS-CoV-2 Omicron variant quickly spread globally, also in regions with high vaccination coverage. Vaccine-induced immunity protects against severe disease, however, the understanding of immunological requirements for protection against Omicron breakthrough infection is limited.

Methods: A matched case-control study was conducted to characterize Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Omicron spike-specific IgG levels, ACE2-blocking antibody titers, and T cell responses were evaluated in samples collected prior to a positive (case) or negative (control) PCR test. Pre- to post-infection nucleocapsid IgG levels among cases were determined to investigate seroconversion.

Findings: A total of 482 cases with Omicron breakthrough infection were matched with 482 uninfected controls. Omicron spike-specific IgG levels were significantly lower in cases compared to controls (geometric mean ratio [95% CI] for BA.2: 0·83 [0·73–0·95], P=0·006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of Omicron breakthrough infection (adjusted odds ratio [95% CI] for BA.2 spike-specific IgG: 0·65 [0·48–0·88], P=0·006 and BA.2 ACE2-blocking antibodies: 0·46 [0·30–0·69], P=0·0002). A sex-stratified analysis revealed that these associations were more pronounced for females than males. No significant differences in frequency of spike-specific T cells were observed. Nucleocapsid IgG seroconversion occurred in 96·9% of cases and we found no correlation between vaccine-induced immunity and seroconversion.

Interpretation: High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new emerging variants and to estimate the necessity and timing of booster vaccination.

Funding: ENFORCE has received a grant from the Danish Ministry of Health (SUM).

Declaration of Interest: NBS declares to have served as an investigator in clinical trials sponsored by Pfizer, Gilead, and Bavarian Nordic. HN declares to have been on advisory boards for GSK and MSD. TB declares receipt of unrestricted grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Foundation, Erik and Susanna Olesen’s Charitable Fund, GSK, Pfizer, Gilead Sciences, and MSD; and being advisory board member for GSK, Pfizer, Gilead Sciences, MSD, Janssen, and Astra Zeneca; and being principal investigator on clinical trials conducted by Pfizer, Boehringer Ingelheim, Gilead Sciences, MSD, Roche, Novartis, Kancera AB, Bavarian Nordic, and Janssen; and being board member on Pentabase; and receiving consulting fees from GSK and Pfizer; and receiving honorarium for lectures from GSK, Pfizer, Gilead Sciences, Boehringer Ingelheim, Abbvie, Astra Zeneca, and Bavarian Nordic; and receiving donation of trial medication (baricitinib) from Eli Lilly. MT declares to be on a Data Safety Monitoring Board for ImmunoCore clinical trial, testing a bispecific T cell engager in people living with HIV. The remaining authors declare no competing interests.

Ethical Approval: The study involved human participants and the protocol was approved by the Danish Medicines Agency (#2020-006003-42) and the National Committee on Health Research Ethics (#1-10-72-337-20). All participants provided written informed consent.

Keywords: SARS-CoV-2, Omicron, COVID-19, Breakthrough Infection, Antibodies, Vaccination, Seroconversion, Case-Control

Suggested Citation

Baerends, Eva and Hvidt, Astrid Korning and Reekie, Joanne and Søgaard, Ole S. and Stærke, Nina Breinholt and Raben, Dorthe and Nielsen, Henrik and Petersen, Kristine Toft and Juhl, Maria Ruwald and Johansen, Isik S. and Lindvig, Susan Olaf and Madsen, Lone Wulff and Wiese, Lothar and Knudsen, Lene Surland and Iversen, Mette Brouw and Benfield, Thomas and Iversen, Kasper Karmark and Andersen, Sidsel Dahl and Juhl, Anna Karina and Dietz, Lisa Loksø and Andreasen, Signe Rode and Fischer, Thea K. and Erikstrup, Christian and Valentiner-Branth, Palle and Lundgren, Jens and Østergaard, Lars Jørgen and Tolstrup, Martin, SARS-CoV-2 Vaccine-Induced Antibodies Protect Against Omicron Breakthrough Infection. Available at SSRN: https://ssrn.com/abstract=4366875 or http://dx.doi.org/10.2139/ssrn.4366875

Eva Baerends

Aarhus University - Department of Infectious Diseases

Astrid Korning Hvidt (Contact Author)

Aarhus University - Department of Infectious Diseases ( email )

Joanne Reekie

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP ( email )

Copenhagen, DK-2100
Denmark

Ole S. Søgaard

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Nina Breinholt Stærke

Aarhus University - Department of Infectious Diseases ( email )

Dorthe Raben

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP ( email )

Henrik Nielsen

Aalborg University - Department of Infectious Diseases ( email )

Aalborg
Denmark

Kristine Toft Petersen

Aalborg University - Department of Infectious Diseases ( email )

Maria Ruwald Juhl

Aalborg University - Department of Infectious Diseases ( email )

Aalborg
Denmark

Isik S. Johansen

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Susan Olaf Lindvig

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Lone Wulff Madsen

Odense University Hospital - Department of Infectious Diseases ( email )

Odense
Denmark

Lothar Wiese

Zealand University Hospital - Department of Infectious Diseases ( email )

Roskilde
Denmark

Lene Surland Knudsen

Zealand University Hospital - Department of Medicine ( email )

Roskilde
Denmark

Mette Brouw Iversen

Zealand University Hospital - Department of Medicine ( email )

Roskilde
Denmark

Thomas Benfield

University of Copenhagen - Department of Infectious Diseases

Copenhagen
Denmark

Kasper Karmark Iversen

University of Copenhagen - Department of Cardiology ( email )

Herlev
Denmark

Sidsel Dahl Andersen

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Anna Karina Juhl

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Lisa Loksø Dietz

Aarhus University - Department of Infectious Diseases ( email )

Signe Rode Andreasen

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Thea K. Fischer

University of Copenhagen - Department of Public Health ( email )

Denmark

Christian Erikstrup

Aarhus University - Department of Clinical Immunology ( email )

Aarhus
Denmark

Palle Valentiner-Branth

Statens Serum Institut - Infectious Disease Epidemiology & Prevention

Jens Lundgren

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections CHIP ( email )

Copenhagen, DK-2100
Denmark

Lars Jørgen Østergaard

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Martin Tolstrup

Aarhus University - Department of Infectious Diseases ( email )

Aarhus
Denmark

Click here to go to TheLancet.com

Paper statistics

Downloads
88
Abstract Views
451
PlumX Metrics