{"doi":"10.17615/7shx-dj40","title":"HIV-Specific Functional Antibody Responses in Breast Milk Mirror Those in Plasma and Are Primarily Mediated by IgG Antibodies","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.","journal":"UNC Libraries","year":2020,"id":112706,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9654,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":327283,"name":"D. C. Montefiori","orcid":null,"position":1,"is_corresponding":false},{"id":403320,"name":"G. M. 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Wilks","orcid":null,"position":12,"is_corresponding":false},{"id":533910,"name":"Grace Overman","orcid":null,"position":13,"is_corresponding":false},{"id":521586,"name":"T. Mahlokozera","orcid":null,"position":14,"is_corresponding":false},{"id":521582,"name":"L. Kalilani","orcid":null,"position":15,"is_corresponding":false},{"id":403330,"name":"S. R. Meshnick","orcid":null,"position":16,"is_corresponding":false},{"id":521584,"name":"T. N. Denny","orcid":null,"position":17,"is_corresponding":false},{"id":521580,"name":"R. V. Lovingood","orcid":null,"position":18,"is_corresponding":false},{"id":442825,"name":"B. H. Hahn","orcid":null,"position":19,"is_corresponding":false},{"id":533911,"name":"G. Ferrari","orcid":null,"position":20,"is_corresponding":false},{"id":521585,"name":"S. R. Permar","orcid":null,"position":21,"is_corresponding":false},{"id":533908,"name":"J. 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