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

Frontiers in Immunology

Christine A. Arocena¹  Kasey Hernandez¹  Michelle Rojas¹  Marcella Sarzotti-Kelsoe³  Georgia D. Tomaras⁴  David Beaumont⁵  Jack Heptinstall⁵  Martina S. Wesley⁵  Kelly E. Seaton⁵  Sheetal Sawant⁵  Nicole L. Yates⁵  Kelvin T. Chiong⁵  Jonathan Hare⁷  Katherine Crisafi⁷  Joseph Nkolola⁸  Dan H. Barouch⁸ 

[1] Center for Human Systems Immunology, Duke University, Durham, NC, United States;Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, United States;Department of Immunology, Duke University, Durham, NC, United States;Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, United States;Department of Surgery, Duke University, Durham, NC, United States;International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom;International AIDS Vaccine Initiative (IAVI), New York, NY, United States;Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States;

关键词: antibody;    immunoprophilaxis;    HIV - human immunodeficiency virus;    pharmacokinetics;    validation;    broadly neutralizing antibodies;   

DOI  :  10.3389/fimmu.2021.709994

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown