Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys

• DOI: 10.1038/s41385-018-0067-7
• Publication Date: 2018-08-16T09:41:40Z
• Authors: Jonathon E. Himes; Ria Goswami; Riley J. Mangan; Amit Kumar; Thomas L. Jeffries; Joshua A. Eudailey; Holly Heimsath; Quang N. Nguyen; Justin Pollara; Celia LaBranche; Meng Chen; Nathan A. Vanderg...; James W. Peacock; Faith Schiro; Cecily Midkiff; Guido Ferrari; David C. Montefiori; Xavier Alvarez He...; Pyone Pyone Aye; Sallie R. Permar
• Keywords: Passive immunity; Polyclonal antibodies

Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born untreated HIV-infected mothers become infected. This study assessed protective capacity natural envelope-specific antibodies isolated from women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and maternal antibody transfer, RMs were i.v. infused orally treated at time with a single weakly neutralizing monoclonal (mAb), tri-mAb cocktail ADCC functionalities, or anti-influenza control mAb. Of these groups, fewest tri-mAb-treated had detectable plasma tissues (2/6, 5/6, 7/8 animals infected tri-mAb, single-mAb, control-mAb respectively). Tri-mAb-treated demonstrated significantly fewer transmitted/founder variants reduced peripheral CD4+ T cell proviral loads 8 weeks post-challenge compared mAb-treated infants. Abortive infection was observed as provirus non-viremic mAb- mAb-, but not animals. These results suggest that polyfunctional contribute inefficiency through vaccinations eliciting non-neutralizing responses could reduce postnatal transmission.