Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 20;231(2):424-434.
doi: 10.1093/infdis/jiae486.

Evaluation and Real-world Experience of a Neutralization Susceptibility Screening Assay for Broadly Neutralizing Anti-HIV-1 Antibodies

Marie Høst Pahus  1 , Yu Zheng  2 , Maxine Olefsky  2 , Jesper Damsgaard Gunst  1 , Pablo Tebas  3 , Babafemi Taiwo  4 , Ole S Søgaard  1 , Michael J Peluso  5 , Yolanda Lie  6 , Jacqueline D Reeves  6 , Christos J Petropoulos  6 , Marina Caskey  7 , Katharine J Bar  3
Affiliations

Evaluation and Real-world Experience of a Neutralization Susceptibility Screening Assay for Broadly Neutralizing Anti-HIV-1 Antibodies

Marie Høst Pahus et al. J Infect Dis. .

Abstract

Background: Development of a screening assay for the clinical use of broadly neutralizing antibodies (bnAbs) is a priority for HIV therapy and cure initiatives.

Methods: We assessed the PhenoSense Monoclonal Antibody Assay (Labcorp-Monogram Biosciences), which is Clinical Laboratory Improvement Amendments (CLIA) validated and has been used prospectively and retrospectively in multiple recent bnAb clinical trials.

Results: When performed on plasma and longitudinal peripheral blood mononuclear cell samples (before and during antiretroviral therapy, respectively), as sourced from a recent clinical trial, the PhenoSense assay produced robust reproducibility, concordance across sample types, and expected ranges in the susceptibility measures of bnAbs in clinical development. When applied retrospectively to baseline samples from 3 recent studies, the PhenoSense assay correlated with published laboratory-based study evaluations, but baseline bnAb susceptibility was not consistently predictive of durable virus suppression. Assessment of assay feasibility in 4 recent clinical studies provides estimates of assay success rate and processing time.

Conclusions: The PhenoSense Monoclonal Antibody Assay provides reproducible bnAb susceptibility measurements across relevant sample types yet is not consistently predictive of virus suppression. Logistical and operational assay requirements can affect timely clinical trial conduct. These results inform bnAb studies in development.

Keywords: HIV; broadly neutralizing antibodies; clinical trials; screening assays.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. Y. L., J. D. R., and C. J. P. are employees of Monogram Biosciences and shareholders of LabCorp, its parent company. 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.

References

    1. Gunst JD, Højen JF, Pahus MH, et al. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nat Med 2023; 29:2547–58. - PMC - PubMed
    1. Rosás-Umbert M, Gunst JD, Pahus MH, et al. Administration of broadly neutralizing anti-HIV-1 antibodies at ART initiation maintains long-term CD8(+) T cell immunity. Nat Commun 2022; 13:6473. - PMC - PubMed
    1. Gunst JD, Pahus MH, Rosás-Umbert M, et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial. Nat Med 2022; 28:2424–35. - PMC - PubMed
    1. Mendoza P, Gruell H, Nogueira L, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature 2018; 561:479–84. - PMC - PubMed
    1. Cohen YZ, Lorenzi JCC, Krassnig L, et al. Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117. J Exp Med 2018; 215:2311–24. - PMC - PubMed

Publication types

MeSH terms