Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants

Autor: Yunda Huang, Lily Zhang, Amanda Eaton, Nonhlanhla N. Mkhize, Lindsay N. Carpp, Erika Rudnicki, Allan DeCamp, Michal Juraska, April Randhawa, Adrian McDermott, Julie Ledgerwood, Philip Andrew, Shelly Karuna, Srilatha Edupuganti, Nyaradzo Mgodi, Myron Cohen, Lawrence Corey, John Mascola, Peter B. Gilbert, Lynn Morris, David C. Montefiori
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Human Vaccines & Immunotherapeutics, Vol 18, Iss 1 (2022)
Druh dokumentu: article
ISSN: 2164-5515
2164-554X
21645515
DOI: 10.1080/21645515.2021.1908030
Popis: VRC01 is being evaluated in the AMP efficacy trials, the first assessment of a passively administered broadly neutralizing monoclonal antibody (bnAb) for HIV-1 prevention. A key analysis will assess serum VRC01-mediated neutralization as a potential correlate of protection. To prepare for this analysis, we conducted a pilot study where we measured longitudinal VRC01 serum concentrations and serum VRC01-mediated neutralization in 47 and 31 HIV-1 uninfected AMP participants, respectively. We applied four different statistical approaches to predict serum VRC01-mediated neutralization titer against Env-pseudotyped viruses, including breakthrough viruses isolated from AMP placebo recipients who became HIV-1 infected during the trial, using VRC01 serum concentration and neutralization potency (IC50 or IC80) of the VRC01 clinical lot against the same virus. Approaches 3 and 4, which utilized pharmacokinetics/pharmacodynamics joint modeling of concentration and neutralization titer, generally performed the best or comparably to Approaches 1 and 2, which, respectively, utilized only measured and model-predicted concentration. For prediction of ID80 titers against breakthrough viruses, Approaches 1 and 2 rendered comparable performance to Approaches 3 and 4, and could be reasonable approaches to adopt in practice as they entail reduced assay cost and less complicated statistical analysis. Our results may be applied to future studies of other bnAbs and bnAb combinations to maximize resource efficiency in serum neutralization titer measurement.
Databáze: Directory of Open Access Journals
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