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

Mucosal Immunol. 2018 Nov;11(6):1716-1726. doi: 10.1038/s41385-018-0067-7. Epub 2018 Aug 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal / blood
  • CD4-Positive T-Lymphocytes / immunology*
  • Disease Models, Animal
  • Disease Transmission, Infectious
  • Female
  • HIV Antibodies / blood
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV-1 / pathogenicity
  • HIV-1 / physiology*
  • Humans
  • Immunization, Passive
  • Macaca mulatta / immunology*
  • Milk, Human / virology*
  • Viral Load

Substances

  • Antibodies, Monoclonal
  • HIV Antibodies