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J Immunol Methods. 2020 Jan 7:112736. doi: 10.1016/j.jim.2020.112736. [Epub ahead of print]

Optimization and qualification of a functional anti-drug antibody assay for HIV-1 bnAbs.

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: mseaman@bidmc.harvard.edu.
2
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
3
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
4
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
5
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
6
PlantVax Corporation, Rockville, MD, USA.
7
Department of Surgery, Duke University Medical Center, Durham, NC, USA; Department of Immunology, Duke University Medical Center, Durham, NC, USA.

Abstract

The recent identification of human monoclonal antibodies with broad and potent neutralizing activity against HIV-1 (bnAbs) has resulted in substantial efforts to develop these molecules for clinical use in the prevention and treatment of HIV-1 infection. As with any protein therapeutic drug product, it is imperative to have qualified assays that can accurately detect and quantify anti-drug antibodies (ADA) that may develop in patients receiving passive administration of HIV-1 bnAbs. Here, we have optimized and qualified a functional assay to assess the potential of ADA to inhibit the neutralizing function of HIV-1 bnAbs. Using a modified version of the validated TZM-bl HIV-1 neutralization assay, murine anti-idiotype antibodies were utilized to optimize and evaluate parameters of linearity, range, limit of detection, specificity, and precision for measuring inhibitory ADA activity against multiple HIV-1 bnAbs that are in clinical development. We further demonstrate the utility of this assay for detecting naturally occurring ADA responses in non-human primates receiving passive administration of human bnAbs. This functional assay format complements binding-antibody ADA strategies being developed for HIV-1 bnAbs, and when utilized together, will support a multi-tiered approach for ADA testing that is compliant with Good Clinical Laboratory Practice (GCLP) procedures and FDA guidance.

KEYWORDS:

Anti-drug antibody; Broadly neutralizing antibodies; HIV-1

PMID:
31917969
DOI:
10.1016/j.jim.2020.112736
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