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

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.

SUBMITTER: Seaman MS

PROVIDER: S-EPMC7103754 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Seaman Michael S MS Bilska Miroslawa M Ghantous Fadi F Eaton Amanda A LaBranche Celia C CC Greene Kelli K Gao Hongmei H Weiner Joshua A JA Ackerman Margaret E ME Garber David A DA Rosenberg Yvonne J YJ Sarzotti-Kelsoe Marcella M Montefiori David C DC

Journal of immunological methods 20200107

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 hav ...[more]

PMID: 31917969

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Dataset Information

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

Publications

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

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