Monoclonal Antibodies as SARS-CoV-2 Serology Standards: Experimental Validation and Broader Implications for Correlates of Protection

Lili Wang; Paul N. Patrone; Anthony J. Kearsley; Jerilyn R. Izac; Adolfas K. Gaigalas; John C. Prostko; Hyung Joon Kwon; Weichun Tang; Martina Kosikova; Hang Xie; Linhua Tian; Elzafir B. Elsheikh; Edward J. Kwee; Troy Kemp; Simon Jochum; Natalie Thornburg; L. Clifford McDonald; Adi V. Gundlapalli; Sheng Lin-Gibson

doi:10.3390/ijms242115705

International Journal of Molecular Sciences (Oct 2023)

Monoclonal Antibodies as SARS-CoV-2 Serology Standards: Experimental Validation and Broader Implications for Correlates of Protection

Lili Wang,
Paul N. Patrone,
Anthony J. Kearsley,
Jerilyn R. Izac,
Adolfas K. Gaigalas,
John C. Prostko,
Hyung Joon Kwon,
Weichun Tang,
Martina Kosikova,
Hang Xie,
Linhua Tian,
Elzafir B. Elsheikh,
Edward J. Kwee,
Troy Kemp,
Simon Jochum,
Natalie Thornburg,
L. Clifford McDonald,
Adi V. Gundlapalli,
Sheng Lin-Gibson

Affiliations

Lili Wang: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Paul N. Patrone: Applied and Computational Mathematics Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Anthony J. Kearsley: Applied and Computational Mathematics Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Jerilyn R. Izac: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Adolfas K. Gaigalas: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
John C. Prostko: Abbott Laboratories, Abbott Park, IL 60064, USA
Hyung Joon Kwon: Laboratory of Pediatric and Respiratory Viral Diseases, Office of Vaccines Research and Review, Center for Biologics Evaluation, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA
Weichun Tang: Laboratory of Pediatric and Respiratory Viral Diseases, Office of Vaccines Research and Review, Center for Biologics Evaluation, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA
Martina Kosikova: Laboratory of Pediatric and Respiratory Viral Diseases, Office of Vaccines Research and Review, Center for Biologics Evaluation, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA
Hang Xie: Laboratory of Pediatric and Respiratory Viral Diseases, Office of Vaccines Research and Review, Center for Biologics Evaluation, Food and Drug Administration (FDA), Silver Spring, MD 20993, USA
Linhua Tian: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Elzafir B. Elsheikh: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Edward J. Kwee: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA
Troy Kemp: Vaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA
Simon Jochum: Roche Diagnostics GmbH, 82377 Penzberg, Germany
Natalie Thornburg: Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA
L. Clifford McDonald: Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA
Adi V. Gundlapalli: Centers for Disease Control and Prevention (CDC), Atlanta, GA 30329, USA
Sheng Lin-Gibson: Biosystems and Biomaterials Division, National Institute of Standards and Technology (NIST), Gaithersburg, MD 20899, USA

DOI: https://doi.org/10.3390/ijms242115705
Journal volume & issue: Vol. 24, no. 21
p. 15705

Abstract

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COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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