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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Seaman, MS; Bilska, M; Ghantous, F; Eaton, A; LaBranche, CC; Greene, K; Gao, H; Weiner, JA; Ackerman, ME; Garber, DA; Rosenberg, YJ; Sarzotti-Kelsoe, M; Montefiori, DC

Published Date

  • April 2020

Published In

Volume / Issue

  • 479 /

Start / End Page

  • 112736 -

PubMed ID

  • 31917969

Pubmed Central ID

  • PMC7103754

Electronic International Standard Serial Number (EISSN)

  • 1872-7905

Digital Object Identifier (DOI)

  • 10.1016/j.jim.2020.112736


  • eng

Conference Location

  • Netherlands