RT Journal Article
SR Electronic
T1 Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 145524
DO 10.1101/145524
A1 Jonathon E. Himes
A1 Ria Goswami
A1 Riley J. Mangan
A1 Amit Kumar
A1 Thomas L. Jeffries, Jr.
A1 Joshua A. Eudailey
A1 Holly Heimsath
A1 Quang N. Nguyen
A1 Justin Pollara
A1 Celia LaBranche
A1 Meng Chen
A1 Nathan A. Vandergrift
A1 James W. Peacock
A1 Faith Schiro
A1 Cecily Midkiff
A1 Guido Ferrari
A1 David C. Montefiori
A1 Xavier Alvarez-Hernandez
A1 Pyone Pyone Aye
A1 Sallie R. Permar
YR 2017
UL http://biorxiv.org/content/early/2017/06/03/145524.abstract
AB Vertical HIV-1 transmission via breastfeeding is the predominant contributor to pediatric infections that are ongoing in this era of highly effective antiretroviral therapy (ART). Remarkably, only ~10% of infants chronically exposed to the virus via breastfeeding from untreated HIV-infected mothers become infected, suggesting the presence of naturally protective factors in breast milk. HIV-specific maternal antibodies are obvious candidates as potential contributors to this protection. This study assessed the protective capacity of common HIV envelope-specific non-broadly neutralizing antibodies isolated from breast milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. Prior to oral SHIV challenge, infant RMs were i.v. infused with either a single weakly-neutralizing monoclonal antibody (mAb), a tri-mAb cocktail with neutralizing and ADCC functionalities, or an anti-influenza HA control mAb. Of these groups, the fewest tri-mAb-treated infants developed plasma viremia (2/6, 3/6, and 6/8 animals viremic in tri-mAb, single-mAb, and control mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer transmitted/founder SHIV variants in plasma and decreased peripheral CD4+ T cell proviral loads at 8 week post-challenge compared to control mAb-treated infants. Abortive infection was observed as detectable CD4+ T cell provirus in non-viremic control mAb- and single-mAb-, but not tri-mAb-treated animals. Taken together, these results support the potential viability of maternal or infant vaccine strategies that elicit non-broadly neutralizing antibodies to prevent vertical transmission of HIV through breastfeeding.