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
Affiliations
- Martina S. Wesley
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Martina S. Wesley
- Department of Surgery, Duke University, Durham, NC, United States
- Kelvin T. Chiong
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Kelvin T. Chiong
- Department of Surgery, Duke University, Durham, NC, United States
- Kelly E. Seaton
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Kelly E. Seaton
- Department of Surgery, Duke University, Durham, NC, United States
- Christine A. Arocena
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Sheetal Sawant
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Sheetal Sawant
- Department of Surgery, Duke University, Durham, NC, United States
- Jonathan Hare
- International AIDS Vaccine Initiative (IAVI), Human Immunology Laboratory, Imperial College, London, United Kingdom
- Jonathan Hare
- International AIDS Vaccine Initiative (IAVI), New York, NY, United States
- Kasey Hernandez
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Michelle Rojas
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Jack Heptinstall
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Jack Heptinstall
- Department of Surgery, Duke University, Durham, NC, United States
- David Beaumont
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- David Beaumont
- Department of Surgery, Duke University, Durham, NC, United States
- Katherine Crisafi
- International AIDS Vaccine Initiative (IAVI), New York, NY, United States
- Joseph Nkolola
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, United States
- Joseph Nkolola
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- Dan H. Barouch
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, United States
- Dan H. Barouch
- Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- Marcella Sarzotti-Kelsoe
- Department of Surgery, Duke University, Durham, NC, United States
- Marcella Sarzotti-Kelsoe
- Department of Immunology, Duke University, Durham, NC, United States
- Georgia D. Tomaras
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Georgia D. Tomaras
- Department of Surgery, Duke University, Durham, NC, United States
- Georgia D. Tomaras
- Department of Immunology, Duke University, Durham, NC, United States
- Georgia D. Tomaras
- Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, United States
- Nicole L. Yates
- Center for Human Systems Immunology, Duke University, Durham, NC, United States
- Nicole L. Yates
- Department of Surgery, Duke University, Durham, NC, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.709994
- Journal volume & issue
-
Vol. 12
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 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.
Keywords
- antibody
- immunoprophilaxis
- HIV - human immunodeficiency virus
- pharmacokinetics
- validation
- broadly neutralizing antibodies
