Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines.

The development of broadly neutralizing antibody (bnAb)-based therapeutic HIV-1 vaccines and cure concepts depends on monitoring bnAb plasma activity in people with HIV (PWH) on suppressive antiretroviral therapy (ART). To enable this, analytical strategies must be defined to reliably distinguish antibody-based neutralization from drug inhibition. Here, we explore strategies that either utilize drug-resistant viruses or remove drugs from plasma. We develop ART-DEX (ART dissociation and size exclusion), an approach which quantitatively separates drugs from plasma proteins following pH-triggered release allowing accurate definition of antibody-based neutralization. We demonstrate that ART-DEX, alone or combined with ART-resistant viruses, provides a highly effective and scalable means of assessing antibody neutralization during ART. Implementation of ART-DEX in standard neutralization protocols should be considered to enhance the analytical capabilities of studies evaluating bnAb therapeutics and therapeutic vaccines, furthering the development of advanced ART and HIV-1 cure strategies.

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Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests A.T. has received unrelated unrestricted research grants from the SNSF, Bill and Melinda Gates Foundation, Gilead Sciences, Novartis Biomedical Research Foundation, University of Zurich (UZH) Foundation, UZH Clinical Research Priority Program, the SHCS, honoraria from Roche Diagnostics and the Institute for biomedical research Bellinzona for consultant and scientific board activity, and directs the Swiss National Reference Center for Retroviruses together with M.H. H.F.G. has received unrelated unrestricted research grants from the SNSF, the SHCS, Yvonne Jacob Foundation, University of Zurich Clinical Research Priority Program, Systems.X, the National Institutes of Health, Gilead Sciences, and Roche. H.F.G. has further received personal fees from Merck, Gilead Sciences, ViiV, Janssen, GSK, Johnson and Johnson, and Novartis for consultancy or DSMB membership and a travel grant from Gilead. M.H. directs the Swiss National Reference Center for Retroviruses and has received unrelated unrestricted research grant from the UZH Clinical Research Priority Program, the SNSF, the SHCS, and the ETH PHRT. I.A.A. has received honoraria from MSD and Sanofi, a travel grant from Gilead Sciences, a grant from ProMedica Foundation, and she is member of the EKIF (Eidgenössische Kommission für Impffragen) of the Federal Office of Public Health. R.D.K. has received grants from SNSF, the National Institutes of Health, and Gilead Sciences.