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Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS
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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422903/ https://www.ncbi.nlm.nih.gov/pubmed/34504492 http://dx.doi.org/10.3389/fimmu.2021.709994 |
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author | Wesley, Martina S. Chiong, Kelvin T. Seaton, Kelly E. Arocena, Christine A. Sawant, Sheetal Hare, Jonathan Hernandez, Kasey Rojas, Michelle Heptinstall, Jack Beaumont, David Crisafi, Katherine Nkolola, Joseph Barouch, Dan H. Sarzotti-Kelsoe, Marcella Tomaras, Georgia D. Yates, Nicole L. |
author_facet | Wesley, Martina S. Chiong, Kelvin T. Seaton, Kelly E. Arocena, Christine A. Sawant, Sheetal Hare, Jonathan Hernandez, Kasey Rojas, Michelle Heptinstall, Jack Beaumont, David Crisafi, Katherine Nkolola, Joseph Barouch, Dan H. Sarzotti-Kelsoe, Marcella Tomaras, Georgia D. Yates, Nicole L. |
author_sort | Wesley, Martina S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8422903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84229032021-09-08 Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS Wesley, Martina S. Chiong, Kelvin T. Seaton, Kelly E. Arocena, Christine A. Sawant, Sheetal Hare, Jonathan Hernandez, Kasey Rojas, Michelle Heptinstall, Jack Beaumont, David Crisafi, Katherine Nkolola, Joseph Barouch, Dan H. Sarzotti-Kelsoe, Marcella Tomaras, Georgia D. Yates, Nicole L. Front Immunol Immunology 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. Frontiers Media S.A. 2021-08-24 /pmc/articles/PMC8422903/ /pubmed/34504492 http://dx.doi.org/10.3389/fimmu.2021.709994 Text en Copyright © 2021 Wesley, Chiong, Seaton, Arocena, Sawant, Hare, Hernandez, Rojas, Heptinstall, Beaumont, Crisafi, Nkolola, Barouch, Sarzotti-Kelsoe, Tomaras and Yates https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Wesley, Martina S. Chiong, Kelvin T. Seaton, Kelly E. Arocena, Christine A. Sawant, Sheetal Hare, Jonathan Hernandez, Kasey Rojas, Michelle Heptinstall, Jack Beaumont, David Crisafi, Katherine Nkolola, Joseph Barouch, Dan H. Sarzotti-Kelsoe, Marcella Tomaras, Georgia D. Yates, Nicole L. Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS |
title | Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS |
title_full | Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS |
title_fullStr | Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS |
title_full_unstemmed | Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS |
title_short | Validation of a Triplex Pharmacokinetic Assay for Simultaneous Quantitation of HIV-1 Broadly Neutralizing Antibodies PGT121, PGDM1400, and VRC07-523-LS |
title_sort | validation of a triplex pharmacokinetic assay for simultaneous quantitation of hiv-1 broadly neutralizing antibodies pgt121, pgdm1400, and vrc07-523-ls |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422903/ https://www.ncbi.nlm.nih.gov/pubmed/34504492 http://dx.doi.org/10.3389/fimmu.2021.709994 |
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