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Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity

Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposur...

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Autores principales: Shapiro, Mariya B., Cheever, Tracy, Malherbe, Delphine C., Pandey, Shilpi, Reed, Jason, Yang, Eun Sung, Wang, Keyun, Pegu, Amarendra, Chen, Xuejun, Siess, Don, Burke, David, Henderson, Heidi, Lewinsohn, Rebecca, Fischer, Miranda, Stanton, Jeffrey J., Axthelm, Michael K., Kahl, Christoph, Park, Byung, Lewis, Anne D., Sacha, Jonah B., Mascola, John R., Hessell, Ann J., Haigwood, Nancy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946664/
https://www.ncbi.nlm.nih.gov/pubmed/31911610
http://dx.doi.org/10.1038/s41467-019-13972-y
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author Shapiro, Mariya B.
Cheever, Tracy
Malherbe, Delphine C.
Pandey, Shilpi
Reed, Jason
Yang, Eun Sung
Wang, Keyun
Pegu, Amarendra
Chen, Xuejun
Siess, Don
Burke, David
Henderson, Heidi
Lewinsohn, Rebecca
Fischer, Miranda
Stanton, Jeffrey J.
Axthelm, Michael K.
Kahl, Christoph
Park, Byung
Lewis, Anne D.
Sacha, Jonah B.
Mascola, John R.
Hessell, Ann J.
Haigwood, Nancy L.
author_facet Shapiro, Mariya B.
Cheever, Tracy
Malherbe, Delphine C.
Pandey, Shilpi
Reed, Jason
Yang, Eun Sung
Wang, Keyun
Pegu, Amarendra
Chen, Xuejun
Siess, Don
Burke, David
Henderson, Heidi
Lewinsohn, Rebecca
Fischer, Miranda
Stanton, Jeffrey J.
Axthelm, Michael K.
Kahl, Christoph
Park, Byung
Lewis, Anne D.
Sacha, Jonah B.
Mascola, John R.
Hessell, Ann J.
Haigwood, Nancy L.
author_sort Shapiro, Mariya B.
collection PubMed
description Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.
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spelling pubmed-69466642020-01-09 Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity Shapiro, Mariya B. Cheever, Tracy Malherbe, Delphine C. Pandey, Shilpi Reed, Jason Yang, Eun Sung Wang, Keyun Pegu, Amarendra Chen, Xuejun Siess, Don Burke, David Henderson, Heidi Lewinsohn, Rebecca Fischer, Miranda Stanton, Jeffrey J. Axthelm, Michael K. Kahl, Christoph Park, Byung Lewis, Anne D. Sacha, Jonah B. Mascola, John R. Hessell, Ann J. Haigwood, Nancy L. Nat Commun Article Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48 h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30–48 h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed. Nature Publishing Group UK 2020-01-07 /pmc/articles/PMC6946664/ /pubmed/31911610 http://dx.doi.org/10.1038/s41467-019-13972-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shapiro, Mariya B.
Cheever, Tracy
Malherbe, Delphine C.
Pandey, Shilpi
Reed, Jason
Yang, Eun Sung
Wang, Keyun
Pegu, Amarendra
Chen, Xuejun
Siess, Don
Burke, David
Henderson, Heidi
Lewinsohn, Rebecca
Fischer, Miranda
Stanton, Jeffrey J.
Axthelm, Michael K.
Kahl, Christoph
Park, Byung
Lewis, Anne D.
Sacha, Jonah B.
Mascola, John R.
Hessell, Ann J.
Haigwood, Nancy L.
Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
title Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
title_full Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
title_fullStr Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
title_full_unstemmed Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
title_short Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
title_sort single-dose bnab cocktail or abbreviated art post-exposure regimens achieve tight shiv control without adaptive immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946664/
https://www.ncbi.nlm.nih.gov/pubmed/31911610
http://dx.doi.org/10.1038/s41467-019-13972-y
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