SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection

Eva A M Baerends; Astrid K Hvidt; Joanne Reekie; Ole S Søgaard; Nina B Stærke; Dorthe Raben; Henrik Nielsen; Kristine T Petersen; Maria R Juhl; Isik S Johansen; Susan O Lindvig; Lone W Madsen; Lothar Wiese; Lene S Knudsen; Mette B Iversen; Thomas Benfield; Kasper K Iversen; Sidsel D Andersen; Anna K Juhl; Lisa L Dietz; Signe R Andreasen; Thea K Fischer; Christian Erikstrup; Palle Valentiner-Branth; Jens Lundgren; Lars Østergaard; Martin Tolstrup; ENFORCE Study Group

doi:10.1016/j.isci.2023.107621

SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection

iScience. 2023 Aug 14;26(9):107621. doi: 10.1016/j.isci.2023.107621. eCollection 2023 Sep 15.

Authors

Eva A M Baerends^{1

2}, Astrid K Hvidt^{1

2}, Joanne Reekie³, Ole S Søgaard^{1

2}, Nina B Stærke^{1

2}, Dorthe Raben³, Henrik Nielsen^{4

5}, Kristine T Petersen⁴, Maria R Juhl⁴, Isik S Johansen^{6

7}, Susan O Lindvig^{6

7}, Lone W Madsen^{6

7}, Lothar Wiese⁸, Lene S Knudsen⁸, Mette B Iversen⁸, Thomas Benfield^{9

10}, Kasper K Iversen^{9

11}, Sidsel D Andersen^{1

2}, Anna K Juhl^{1

2}, Lisa L Dietz^{1

2}, Signe R Andreasen^{1

2}, Thea K Fischer^{10

12}, Christian Erikstrup^{2

13}, Palle Valentiner-Branth¹⁴, Jens Lundgren^{3

10

15}, Lars Østergaard^{1

2}, Martin Tolstrup^{1

2}; ENFORCE Study Group

Collaborators

ENFORCE Study Group:
J Lundgren, L Østergaard, T Benfield, L Krohn-Dehli, D K Petersen, K Fogh, E Højmark, K K Iversen, P Bek, V Klastrup, F Larsen, S H Rasmussen, M H Schleimann, S Schieber, N B Stærke, A Søndergaard, B Tarp, M Tousgaard, Y Yehdego, J Bodilsen, H Nielsen, K T Petersen, M Ruwald, R K Thisted, S F Caspersen, M Iversen, L S Knudsen, J L Meyerhoff, L G Sander, L Wiese, C Abildgaard, I K Holden, N E Johansen, I S Johansen, L Larsen, S O Lindvig, L W Madsen, A Øvrehus, N A Kruse, H Lomholdt, T G Krause, P Valentiner-Branth, B Søborg, T K Fischer, C Erikstrup, S R Ostrowski, M Tolstrup, O S Søgaard, D Raben, E Jylling, D Hougaard, S D Andersen, K Lykkegaard, S R Andreasen, E Baerends, L L Dietz, A K Hvidt, A K Juhl, R Olesen, K K Andersen, W Bannister, C Bjernved, T W Elsing, F V Esmann, M A Ghafari, E Gravholdt, S F Jakobsen, M L Jakobsen, C M Jensen, T Ø Jensen, D Kristensen, L R Kumar, C Matthews, N Normand, C Olsson, J Reekie, A Traytel, T Weide, A M Hvas, H Støvring

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 Departments of Clinical Medicine and Public Health, University of Copenhagen, Copenhagen, Denmark.
¹¹ Department of Cardiology and Emergency Medicine, Herlev Hospital, Herlev, Denmark.
¹² Department of Clinical Research, Nordsjællands University Hospital, Hillerød, Denmark.
¹³ Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
¹⁴ Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.
¹⁵ Department of Infectious Diseases, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

Abstract

SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection. The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [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 infection (aOR [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 showed more pronounced associations for females than males. 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 variants and to estimate the necessity and timing of booster vaccination.

Keywords: Immune response; Immunology; Molecular medicine.