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Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda

Authors
Journal
Journal of Infection
0163-4453
Publisher
Elsevier
Volume
68
Issue
3
Identifiers
DOI: 10.1016/j.jinf.2013.11.002
Keywords
  • Breast Milk
  • Hiv
  • Neutralization
  • Igg
  • Iga
  • Uganda
  • Subtype A
  • Subtype D
  • Mucosal Immunity

Abstract

Summary 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.

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