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Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques

Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-d...

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Autores principales: Rosenberg, Yvonne J., Montefiori, David C., LaBranche, Celia C., Lewis, Mark G., Sack, Markus, Lees, Jonathan P., Jiang, Xiaoming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816452/
https://www.ncbi.nlm.nih.gov/pubmed/27031108
http://dx.doi.org/10.1371/journal.pone.0152760
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author Rosenberg, Yvonne J.
Montefiori, David C.
LaBranche, Celia C.
Lewis, Mark G.
Sack, Markus
Lees, Jonathan P.
Jiang, Xiaoming
author_facet Rosenberg, Yvonne J.
Montefiori, David C.
LaBranche, Celia C.
Lewis, Mark G.
Sack, Markus
Lees, Jonathan P.
Jiang, Xiaoming
author_sort Rosenberg, Yvonne J.
collection PubMed
description Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention.
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spelling pubmed-48164522016-04-14 Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques Rosenberg, Yvonne J. Montefiori, David C. LaBranche, Celia C. Lewis, Mark G. Sack, Markus Lees, Jonathan P. Jiang, Xiaoming PLoS One Research Article Intravascular delivery of broadly neutralizing antibodies (bnAbs) has shown promise for prevention and treatment of HIV infection. However, multiple IV administrations in geographic locations with poor accessibility to medical care have practical limitations. We have assessed the efficacy of plant-derived PGT121 delivered subcutaneously (SC) against pre-and post-intravaginal challenge using a rigorous SHIV-SF162P3 macaque protection model. SC administered PGT121 exhibited a longer serum half-life than IV administration and was more consistent than intramuscular delivery. A dose of 3.5mg/kg PGT121 prevented infection at a minimum ID50 neutralization titer of 1:295 while 5mg/kg protected five of six macaques when delivered immediately post-challenge. These results suggest the utility of plant-derived bnAbs delivered SC for HIV prevention. Public Library of Science 2016-03-31 /pmc/articles/PMC4816452/ /pubmed/27031108 http://dx.doi.org/10.1371/journal.pone.0152760 Text en © 2016 Rosenberg et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rosenberg, Yvonne J.
Montefiori, David C.
LaBranche, Celia C.
Lewis, Mark G.
Sack, Markus
Lees, Jonathan P.
Jiang, Xiaoming
Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
title Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
title_full Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
title_fullStr Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
title_full_unstemmed Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
title_short Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques
title_sort protection against shiv challenge by subcutaneous administration of the plant-derived pgt121 broadly neutralizing antibody in macaques
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816452/
https://www.ncbi.nlm.nih.gov/pubmed/27031108
http://dx.doi.org/10.1371/journal.pone.0152760
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