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

Jana M. Palaia, Michelle McConnell, Jenna E. Achenbach, Claire E. Gustafson, Kristina A. Stoermer, Monica Nolan, Laura A. Guay, Thomas K. Leitner, Flavia Matovu, Allan W. Taylor, Mary Glenn Fowler, Edward N. Janoff

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalJournal of Infection
Volume68
Issue number3
DOIs
StatePublished - Mar 1 2014

Keywords

  • Breast milk
  • HIV
  • IgG, IgA
  • Mucosal immunity
  • Neutralization
  • Subtype A
  • Subtype D
  • Uganda

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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  • Cite this

    Palaia, J. M., McConnell, M., Achenbach, J. E., Gustafson, C. E., Stoermer, K. A., Nolan, M., Guay, L. A., Leitner, T. K., Matovu, F., Taylor, A. W., Fowler, M. G., & Janoff, E. N. (2014). Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda. Journal of Infection, 68(3), 264-272. https://doi.org/10.1016/j.jinf.2013.11.002