Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Sep 10

PMID 34504492

Citations 7

Authors

Martina S Wesley

Kelvin T Chiong

Kelly E Seaton

Christine A Arocena

Sheetal Sawant

Jonathan Hare

Kasey Hernandez

Michelle Rojas

Jack Heptinstall

David Beaumont

Katherine Crisafi

Joseph Nkolola

Dan H Barouch

Marcella Sarzotti-Kelsoe

Georgia D Tomaras

Nicole L Yates

Affiliations

Soon will be listed here.

Abstract

The outcome of the recent Antibody Mediated Prevention (AMP) trials that tested infusion of the broadly neutralizing antibody (bnAb) VRC01 provides proof of concept for blocking infection from sensitive HIV-1 strains. These results also open up the possibility that triple combinations of bnAbs such as PGT121, PGDM1400, as well as long-lasting LS variants such as VRC07-523 LS, have immunoprophylactic potential. PGT121 and PGDM1400 target the HIV-1 V3 and V2 glycan regions of the gp120 envelope protein, respectively, while VRC07-523LS targets the HIV-1 CD4 binding site. These bnAbs demonstrate neutralization potency and complementary breadth of HIV-1 strain coverage. An important clinical trial outcome is the accurate measurement of concentrations of passively infused bnAbs to determine effective doses for therapy and/or prevention. Standardization and validation of this testing method is a key element for clinical studies as is the ability to simultaneously detect multiple bnAbs in a specific manner. Here we report the development of a sensitive, specific, accurate, and precise multiplexed microsphere-based assay that simultaneously quantifies the respective physiological concentrations of passively infused bnAbs in human serum to ultimately define the threshold needed for protection from HIV-1 infection.

Citing Articles

Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.

Chawana T, Walsh S, Stranix-Chibanda L, Chirenje Z, Yu C, Zhang L BMC Immunol. 2025; 26(1):8.

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Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage.

Mason R, Zhang B, Morano N, Shen C, McKee K, Heimann A Cell Rep. 2025; 44(1):115223.

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Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human,....

Edupuganti S, Hurt C, Stephenson K, Huang Y, Paez C, Yu C Lancet HIV. 2024; 12(1):e13-e25.

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Recapitulation of HIV-1 Neutralization Breadth in Plasma by the Combination of Two Broadly Neutralizing Antibodies from Different Lineages in the Same SHIV-Infected Rhesus Macaque.

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Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV.

Mayer B, Zhang L, deCamp A, Yu C, Sato A, Angier H Pharmaceutics. 2024; 16(5).

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