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. 2022 Nov 28;226(11):1903-1908.
doi: 10.1093/infdis/jiac321.

Correlation Between Postvaccination Anti-Spike Antibody Titers and Protection Against Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Population-Based Longitudinal Study

Giulia Vivaldi  1   2 , David A Jolliffe  1   2 , Sian Faustini  3 , Adrian M Shields  3 , Hayley Holt  1   2   4 , Natalia Perdek  1 , Mohammad Talaei  2 , Florence Tydeman  1   2 , Emma S Chambers  1 , Weigang Cai  1 , Wenhao Li  1 , Joseph M Gibbons  1 , Corinna Pade  1 , Áine McKnight  1 , Seif O Shaheen  2 , Alex G Richter  3 , Adrian R Martineau  1   2   4
Affiliations

Correlation Between Postvaccination Anti-Spike Antibody Titers and Protection Against Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Population-Based Longitudinal Study

Giulia Vivaldi et al. J Infect Dis. .

Abstract

In this population-based cohort of 7538 adults, combined immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) anti-spike titers measured after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination were predictive of protection against breakthrough SARS-CoV-2 infection. Discrimination was significantly improved by adjustment for factors influencing risk of SARS-CoV-2 exposure, including household overcrowding, public transport use, and visits to indoor public places. Anti-spike IgG/A/M titers showed positive correlation with neutralizing antibody titers (rs = 0.80 [95% confidence interval, .72-.86]; P < .001) and S peptide-stimulated interferon-γ concentrations (rs = 0.31 [.13-.47]; P < .001).

Keywords: SARS-CoV-2; breakthrough infection; combined antibody response; vaccination.

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Conflict of interest statement

Potential conflicts of interest. A. R. M. declares receipt of funding, outside the submitted work, to support vitamin D research from the following companies, which manufacture or sell vitamin D supplements: Pharma Nord, DSM Nutritional Products, Thornton & Ross, and Hyphens Pharma. A. R. M. also declares the following, all outside the submitted work: receipt of funding from the Karl R Pfleger Foundation, the AIM Foundation, the UK National Institute for Health Research Clinical Research Network, Warburtons, and Matthew Isaacs; consulting fees from DSM Nutritional Products and payment from Oregon State University for lectures, presentations, speakers bureaus, manuscript writing, or educational events; support for attending meetings from Pharma Nord and Abiogen Pharma; participation on the data and safety monitoring board for the VITALITY trial (VITamin D for AdoLescents with HIV to reduce musculoskeletal morbidity and ImmunopaThologY); unpaid work as a program committee member for the Vitamin D Workshop; and receipt of vitamin D capsules for clinical trial use from Pharma Nord, Synergy Biologics, and Cytoplan. E. S. C. declares receipt of an honorarium from UCB Pharma for lectures, outside the submitted work, and is an Early Career Trustee for the British Society for Immunology. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Correlation between combined anti-spike immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) and neutralizing antibody (half-maximal inhibitory concentration [IC50]) titers (A) and anti-spike IgG/A/M and interferon (IFN) γ (B), and distribution of anti-spike IgG/A/M titers across the sampling period (C). A, B, Correlation analyses were performed in 113 participants who were fully vaccinated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); distributions are shown with linear regression lines and 95% confidence intervals (CIs). C, Median anti-spike IgG/A/M titers measured at different time points after SAR-CoV-2 vaccination, with interquartile ranges. Horizontal dashed line presents the assay’s limit of detection (LOD). Abbreviations: BAU, binding antibody units; ChAdOx1, ChAdOx1 nCoV-19.
Figure 2.
Figure 2.
Receiver operating characteristic (ROC) curve analysis for breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after SARS-CoV-2 vaccination. ROC curves and area under the ROC curve (AUROC) for combined anti-spike immunoglobulin (Ig) G, IgA, and IgM (IgG/A/M) ratios as a predictor of breakthrough infection, alone or adjusted for variables reflecting SARS-CoV-2 exposure, for all participants with data for included covariates and by vaccine type. Abbreviations: ChAdOx1, ChAdOx1 nCoV-19; CI, confidence interval.
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