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.
authors: Duke Human Vaccine Institute, Duke University Medical Center, Box 103020, Durham, NC 27710, USA.
authors: Genevieve G
authors: GG
authors: Fouda
authors: Nicole L
authors: NL
authors: Yates
authors: Justin
authors: J
authors: Pollara
authors: Xiaoying
authors: X
authors: Shen
authors: Glenn R
authors: GR
authors: Overman
authors: Tatenda
authors: T
authors: Mahlokozera
authors: Andrew B
authors: AB
authors: Wilks
authors: Helen H
authors: HH
authors: Kang
authors: Jesus F
authors: JF
authors: Salazar-Gonzalez
authors: Maria G
authors: MG
authors: Salazar
authors: Linda
authors: L
authors: Kalilani
authors: Steve R
authors: SR
authors: Meshnick
authors: Beatrice H
authors: BH
authors: Hahn
authors: George M
authors: GM
authors: Shaw
authors: Rachel V
authors: RV
authors: Lovingood
authors: Thomas N
authors: TN
authors: Denny
authors: Barton
authors: B
authors: Haynes
authors: Norman L
authors: NL
authors: Letvin
authors: Guido
authors: G
authors: Ferrari
authors: David C
authors: DC
authors: Montefiori
authors: Georgia D
authors: GD
authors: Tomaras
authors: Sallie R
authors: SR
authors: Permar
mesh_terms: D057134:Antibodies, Neutralizing / Q000032:analysis; D000917:Antibody Formation; D000920:Antibody-Dependent Cell Cytotoxicity; D003429:Cross Reactions; D005260:Female; D015483:HIV Antibodies / Q000032:analysis*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis*; D008895:Milk, Human / Q000276:immunology*; D009500:Neutralization Tests; D010949:Plasma / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054299:env Gene Products, Human Immunodeficiency Virus