Objectives: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. Results: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n=5), not IgA, diminished neutralization (mean 78±33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.
Bibliographical noteFunding Information:
This work supported by NIH R01-HD059527 , R01-AI41361 , R01 AI097265 , the United States Centers for Disease Control (CDC; “Pathobiology of Breast Milk among HIV-1 infected Ugandan women receiving intrapartum nevirapine” study), the Elisabeth Glaser Pediatric AIDS Foundation (EGPAF) MV-00-9-900-01432-0-00, University of Colorado Denver's Office of Interdisciplinary Women's Health Research Grant , the Mucosal and Vaccine Research Colorado Program (MAVRC) and the University of Colorado Cancer Center DNA Sequencing and Analysis Core (Grant #P30 CA046934 ). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the United States Centers for Disease Control and Prevention. We thank Jacinta Cooper for technical support and advice and the women in Kampala, Uganda for their participation.
- Breast milk
- IgG, IgA
- Mucosal immunity
- Subtype A
- Subtype D