Frontiers in Immunology (Aug 2021)

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

  • Martina S. Wesley,
  • Martina S. Wesley,
  • Kelvin T. Chiong,
  • Kelvin T. Chiong,
  • Kelly E. Seaton,
  • Kelly E. Seaton,
  • Christine A. Arocena,
  • Sheetal Sawant,
  • Sheetal Sawant,
  • Jonathan Hare,
  • Jonathan Hare,
  • Kasey Hernandez,
  • Michelle Rojas,
  • Jack Heptinstall,
  • Jack Heptinstall,
  • David Beaumont,
  • David Beaumont,
  • Katherine Crisafi,
  • Joseph Nkolola,
  • Joseph Nkolola,
  • Dan H. Barouch,
  • Dan H. Barouch,
  • Marcella Sarzotti-Kelsoe,
  • Marcella Sarzotti-Kelsoe,
  • Georgia D. Tomaras,
  • Georgia D. Tomaras,
  • Georgia D. Tomaras,
  • Georgia D. Tomaras,
  • Nicole L. Yates,
  • Nicole L. Yates

DOI
https://doi.org/10.3389/fimmu.2021.709994
Journal volume & issue
Vol. 12

Abstract

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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 in vivo 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.

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