HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies |
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Authors: | Fouda Genevieve G Yates Nicole L Pollara Justin Shen Xiaoying Overman Glenn R Mahlokozera Tatenda Wilks Andrew B Kang Helen H Salazar-Gonzalez Jesus F Salazar Maria G Kalilani Linda Meshnick Steve R Hahn Beatrice H Shaw George M Lovingood Rachel V Denny Thomas N Haynes Barton Letvin Norman L Ferrari Guido Montefiori David C Tomaras Georgia D Permar Sallie R;Center for HIV/AIDS Vaccine Immunology |
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Institution: | Duke Human Vaccine Institute, Duke University Medical Center, Box 103020, Durham, NC 27710, USA. |
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Abstract: | Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk. |
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