TY - JOUR T1 - Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys JF - bioRxiv DO - 10.1101/145524 SP - 145524 AU - Jonathon E. Himes AU - Ria Goswami AU - Riley J. Mangan AU - Amit Kumar AU - Thomas L. Jeffries, Jr. AU - Joshua A. Eudailey AU - Holly Heimsath AU - Quang N. Nguyen AU - Justin Pollara AU - Celia LaBranche AU - Meng Chen AU - Nathan A. Vandergrift AU - James W. Peacock AU - Faith Schiro AU - Cecily Midkiff AU - Guido Ferrari AU - David C. Montefiori AU - Xavier Alvarez-Hernandez AU - Pyone Pyone Aye AU - Sallie R. Permar Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/03/145524.abstract N2 - 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. ER -