Comparison of vaccine-induced antibody neutralization against SARS-CoV-2 variants of concern following primary and booster doses of COVID-19 vaccines

Astrid K Hvidt; Eva A M Baerends; Ole S Søgaard; Nina B Stærke; Dorthe Raben; Joanne Reekie; Henrik Nielsen; Isik S Johansen; Lothar Wiese; Thomas L Benfield; Kasper K Iversen; Ahmed B Mustafa; Maria R Juhl; Kristine T Petersen; Sisse R Ostrowski; Susan O Lindvig; Line D Rasmussen; Marianne H Schleimann; Sidsel D Andersen; Anna K Juhl; Lisa L Dietz; Signe R Andreasen; Jens Lundgren; Lars Østergaard; Martin Tolstrup; ENFORCE Study Group

doi:10.3389/fmed.2022.994160

Comparison of vaccine-induced antibody neutralization against SARS-CoV-2 variants of concern following primary and booster doses of COVID-19 vaccines

Front Med (Lausanne). 2022 Oct 3:9:994160. doi: 10.3389/fmed.2022.994160. eCollection 2022.

Authors

Astrid K Hvidt^{1

2}, Eva A M Baerends^{1

2}, Ole S Søgaard^{1

2}, Nina B Stærke^{1

2}, Dorthe Raben³, Joanne Reekie³, Henrik Nielsen^{4

5}, Isik S Johansen^{6

7}, Lothar Wiese⁸, Thomas L Benfield^{9

10}, Kasper K Iversen^{10

11}, Ahmed B Mustafa^{9

10}, Maria R Juhl^{4

5}, Kristine T Petersen^{4

5}, Sisse R Ostrowski^{10

12}, Susan O Lindvig^{6

7}, Line D Rasmussen^{6

7}, Marianne H Schleimann^{1

2}, Sidsel D Andersen^{1

2}, Anna K Juhl^{1

2}, Lisa L Dietz^{1

2}, Signe R Andreasen^{1

2}, Jens Lundgren^{3

10

13}, Lars Østergaard^{1

2}, Martin Tolstrup^{1

2}; ENFORCE Study Group

Affiliations

¹ Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
² Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ Center of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.
⁵ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁶ Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
⁷ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁸ Department of Medicine, Zealand University Hospital, Roskilde, Denmark.
⁹ Department of Infectious Diseases, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
¹⁰ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹¹ Deparment of Cardiology and Emergency Medicine, Herlev Hospital, Herlev, Denmark.
¹² Department of Clinical Immunology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
¹³ Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Abstract

The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants.

Keywords: COVID-19; SARS-CoV-2; antibodies; booster; immunity; neutralization; omicron; vaccines.

Copyright © 2022 Hvidt, Baerends, Søgaard, Stærke, Raben, Reekie, Nielsen, Johansen, Wiese, Benfield, Iversen, Mustafa, Juhl, Petersen, Ostrowski, Lindvig, Rasmussen, Schleimann, Andersen, Juhl, Dietz, Andreasen, Lundgren, Østergaard, Tolstrup and the ENFORCE Study Group.