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

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

^*Corresponding author for this work

Medicine (Roskilde)

Research output: Contribution to journal › Article › Research › peer-review

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.

Original language	English
Article number	107621
Number of pages	14
Journal	iScience
Volume	26
Issue number	9
DOIs	https://doi.org/10.1016/j.isci.2023.107621
Publication status	Published - 15 Sept 2023

Funding

ENFORCE has received a grant from the Danish Ministry of Health (SUM) . The ENFORCE study group members all contributed substantially to the study. A full list of members of the ENFORCE study group may be found at https://chip.dk/Research/Studies/ENFORCE/Study-Group. We would like to thank C. Hansen, M. Gram, and P. Valentiner-Branth, who provided a complete dataset of viral variant sequencing data in Denmark through personal communications (November 16th 2022) . These data were utilized in Figure 1B.

Funders
Danish Ministry of Health

Keywords

Covid-19

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Baerends, E. A. M., Hvidt, A. K., Reekie, J., Søgaard, O. S., Stærke, N. B., Raben, D., Nielsen, H., Petersen, K. T., Juhl, M. R., Johansen, I. S., Lindvig, S. O., Madsen, L. W., Wiese, L., Knudsen, L. S., Iversen, M. B., Benfield, T., Iversen, K. K., Andersen, S. D., Juhl, A. K., ... ENFORCE Study Group (2023). SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection. iScience, 26(9), Article 107621. https://doi.org/10.1016/j.isci.2023.107621

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title = "SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection",

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.",

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Baerends, EAM, Hvidt, AK, Reekie, J, Søgaard, OS, Stærke, NB, Raben, D, Nielsen, H, Petersen, KT, Juhl, MR, Johansen, IS, Lindvig, SO, Madsen, LW, Wiese, L , Knudsen, LS , Iversen, MB, Benfield, T, Iversen, KK, Andersen, SD, Juhl, AK, Dietz, LL, Andreasen, SR, Fischer, TK, Erikstrup, C, Valentiner-Branth, P, Lundgren, J, Østergaard, L, Tolstrup, M & ENFORCE Study Group 2023, 'SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection', iScience, vol. 26, no. 9, 107621. https://doi.org/10.1016/j.isci.2023.107621

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T1 - SARS-CoV-2 vaccine-induced antibodies protect against Omicron breakthrough infection

AU - Baerends, Eva A M

AU - Hvidt, Astrid K

AU - Reekie, Joanne

AU - Søgaard, Ole S

AU - Stærke, Nina B

AU - Raben, Dorthe

AU - Nielsen, Henrik

AU - Petersen, Kristine T

AU - Juhl, Maria R

AU - Johansen, Isik S

AU - Lindvig, Susan O

AU - Madsen, Lone W

AU - Wiese, Lothar

AU - Knudsen, Lene S

AU - Iversen, Mette B

AU - Benfield, Thomas

AU - Iversen, Kasper K

AU - Andersen, Sidsel D

AU - Juhl, Anna K

AU - Dietz, Lisa L

AU - Andreasen, Signe R

AU - Fischer, Thea K

AU - Erikstrup, Christian

AU - Valentiner-Branth, Palle

AU - Lundgren, Jens

AU - Østergaard, Lars

AU - Tolstrup, Martin

AU - ENFORCE Study Group

PY - 2023/9/15

Y1 - 2023/9/15

N2 - 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.

AB - 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.

KW - Covid-19

U2 - 10.1016/j.isci.2023.107621

DO - 10.1016/j.isci.2023.107621

M3 - Article

C2 - 37682631

VL - 26

JO - iScience

JF - iScience

IS - 9

M1 - 107621

ER -

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

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