Elsevier

Vaccine

Volume 40, Issue 41, 29 September 2022, Pages 5868-5872
Vaccine

Short communication
Permissive omicron breakthrough infections in individuals with binding or neutralizing antibodies to ancestral SARS-CoV-2

https://doi.org/10.1016/j.vaccine.2022.08.058Get rights and content

Highlights

  • High binding antibody titers and high surrogate neutralizing antibody activity are insufficient markers of protection from breakthrough infection in variants capable of immune escape.

  • Laboratory tests with antigen targets based on Wuhan-Hu-1 may not accurately reflect immune protection from variants with significant differences in the spike protein.

Abstract

Background

Breakthrough infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has occurred in populations with high vaccination rates.

Methods

In a longitudinal cohort study, pre-breakthrough infection sera for Omicron breakthroughs (n = 12) were analyzed. Assays utilized include a laboratory-developed solid phase binding assay to recombinant spike protein, a commercial assay to the S1 domain of the spike protein calibrated to the World Health Organization (WHO) standard, and a commercial solid-phase surrogate neutralizing activity (SNA) assay. All assays employed spike protein preparations based on sequences from the Wuhan-Hu-1 strain.

Results

Pre-breakthrough binding antibody titers ranged from 1:800 to 1:51,200 for the laboratory-developed binding assay, which correlated well and agreed quantitatively with the commercial spike S1 domain WHO calibrated assay. SNA was detected in 10/12 (83%) samples.

Conclusions

Neither high binding titers nor SNA were markers of protection from Omicron infection/re-infection.

Keywords

Binding antibodies
Neutralizing antibodies
SARS-CoV-2
Omicron
Breakthrough

Abbreviations

SNA
surrogate neutralizing activity
UI
No hx of natural infection prior to BT
NI
Hx of natural infection prior to BT
NII
Hx of natural infection 2x prior to BT
V1
Vaccinated once
V2
Vaccinated twice
V3
Vaccinated twice + booster vaccination
BT
Breakthrough infection

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