Title: Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition

226 words) 23 Vertical HIV-1 transmission via breastfeeding is the predominant contributor to pediatric 24 infections that are ongoing in this era of highly effective antiretroviral therapy (ART). 25 Remarkably, only ~10% of infants chronically exposed to the virus via breastfeeding from 26 untreated HIV-infected mothers become infected, suggesting the presence of naturally protective 27 factors in breast milk. HIV-specific maternal antibodies are obvious candidates as potential 28 contributors to this protection. This study assessed the protective capacity of common HIV 29 envelope-specific non-broadly neutralizing antibodies isolated from breast milk of HIV-infected 30 women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. Prior to oral SHIV 31 challenge, infant RMs were i.v. infused with either a single weakly-neutralizing monoclonal 32 antibody (mAb), a tri-mAb cocktail with neutralizing and ADCC functionalities, or an anti33 influenza HA control mAb. Of these groups, the fewest tri-mAb-treated infants developed 34 plasma viremia (2/6, 3/6, and 6/8 animals viremic in tri-mAb, single-mAb, and control mAb 35 groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer 36 transmitted/founder SHIV variants in plasma and decreased peripheral CD4+ T cell proviral 37 loads at 8 week post-challenge compared to control mAb-treated infants. Abortive infection was 38 observed as detectable CD4+ T cell provirus in non-viremic control mAband single-mAb-, but 39 not tri-mAb-treated animals. Taken together, these results support the potential viability of 40 maternal or infant vaccine strategies that elicit non-broadly neutralizing antibodies to prevent 41 vertical transmission of HIV through breastfeeding. 42 43 Importance (150 words) 44 . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/145524 doi: bioRxiv preprint first posted online Jun. 3, 2017;