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

Autor: Himes JE; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Goswami R; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Mangan RJ; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Kumar A; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Jeffries TL Jr; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Eudailey JA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Heimsath H; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Nguyen QN; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Pollara J; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.; Department of Surgery, Duke University School of Medicine, Durham, NC, USA., LaBranche C; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Chen M; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Vandergrift NA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Peacock JW; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Schiro F; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Midkiff C; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Ferrari G; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.; Department of Surgery, Duke University School of Medicine, Durham, NC, USA., Montefiori DC; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA., Hernandez XA; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Aye PP; Tulane National Primate Research Center, Tulane University, Covington, LA, USA., Permar SR; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. sallie.permar@duke.edu.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA. sallie.permar@duke.edu.; Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA. sallie.permar@duke.edu.; Department of Immunology, Duke University School of Medicine, Durham, NC, USA. sallie.permar@duke.edu.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2018 Nov; Vol. 11 (6), pp. 1716-1726. Date of Electronic Publication: 2018 Aug 16.
DOI: 10.1038/s41385-018-0067-7
Abstrakt: Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to untreated HIV-infected mothers become infected. This study assessed the protective capacity of natural HIV envelope-specific antibodies isolated from the milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and milk maternal antibody transfer, infant RMs were i.v. infused and orally treated at the time of challenge with a single weakly neutralizing milk monoclonal antibody (mAb), a tri-mAb cocktail with weakly neutralizing and ADCC functionalities, or an anti-influenza control mAb. Of these groups, the fewest tri-mAb-treated infants had SHIV detectable in plasma or tissues (2/6, 5/6, and 7/8 animals infected in tri-mAb, single-mAb, and control-mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer plasma transmitted/founder variants and reduced peripheral CD4+ T cell proviral loads at 8 weeks 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 in tri-mAb-treated animals. These results suggest that polyfunctional milk antibodies contribute to the natural inefficiency of HIV-1 transmission through breastfeeding and infant vaccinations eliciting non-neutralizing antibody responses could reduce postnatal HIV transmission.
Databáze: MEDLINE
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