@article{4254f80a1ecc46809d2647abd94402a3,
title = "Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity",
abstract = "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.",
author = "Shapiro, {Mariya B.} and Tracy Cheever and Malherbe, {Delphine C.} and Shilpi Pandey and Jason Reed and Yang, {Eun Sung} and Keyun Wang and Amarendra Pegu and Xuejun Chen and Don Siess and David Burke and Heidi Henderson and Rebecca Lewinsohn and Miranda Fischer and Stanton, {Jeffrey J.} and Axthelm, {Michael K.} and Christoph Kahl and Byung Park and Lewis, {Anne D.} and Sacha, {Jonah B.} and Mascola, {John R.} and Hessell, {Ann J.} and Haigwood, {Nancy L.}",
note = "Funding Information: We thank Dr. Ranajit Pal for discussions about quantitation of viral titer, and Drs. Gabriela Webb and Shaheed Abdulhaqq for discussions regarding virus stock production. We acknowledge technical assistance from Philip Barnette and William Sutton. We thank Dr. Rebecca M. Ducore, Lois M.A. Colgin and Heidi L. Pecoraro for performing necropsies and evaluating tissues for the study, and Dr. Peter Barry for kindly providing the cytomegalovirus detection antibody for pathology analyses. We acknowledge the veterinary and technical staff of the Division of Comparative Medicine at the Oregon National Primate Research Center for animal husbandry. This work was supported by NIH R01 HD080459 (N.L.H.), U42 OD023038 (M.K.A.), U42 OD010426 (M.K.A.), and P51 OD011092 (ONPRC), and by the intramural research program of the Vaccine Research Center, NIAID, NIH. M.B.S. was supported by NIH T32 AI007472. Funding Information: Ethics statement. Macaque studies were performed at the Oregon National Primate Research Center (ONPRC) in Beaverton, OR, USA in compliance with all ethical regulations for animal testing and research. The ONPRC is accredited by the American Association for the Accreditation of Laboratory Animal Care (AAALAC) International, and adheres to the Guide for the Care and Use of Laboratory Animals and the U.S. Public Health Service Policy on the Humane Care and Use of Laboratory Animals. The study protocol was approved by the Oregon Health & Science University (OHSU) West Campus Institutional Animal Care and Use Committee (IACUC). Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-019-13972-y",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}