Fouda, GGYates, NLPollara, JShen, XOverman, GRMahlokozera, TWilks, ABKang, HHSalazar-Gonzalez, JFSalazar, MGKalilani, LMeshnick, SRHahn, BHShaw, GMLovingood, RVDenny, TNHaynes, BLetvin, NLFerrari, GMontefiori, DCTomaras, GDPermar, SRImmunology, the Center for HIVAIDS Vaccine2017-06-022017-06-022011-09https://hdl.handle.net/10161/14737Despite 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.Antibodies, NeutralizingAntibody FormationAntibody-Dependent Cell CytotoxicityCross ReactionsFemaleHIV AntibodiesHIV InfectionsHumansImmunoglobulin AImmunoglobulin GMilk, HumanNeutralization TestsPlasmaenv Gene Products, Human Immunodeficiency VirusJournal article1098-5514