Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
BACKGROUND: Generation of potent anti-HIV antibody responses in mucosal compartments is a potential requirement of a transmission-blocking HIV vaccine. HIV-specific, functional antibody responses are present in breast milk, and these mucosal antibody responses may play a role in protection of the majority of HIV-exposed, breastfeeding infants. Therefore, characterization of HIV-specific antibodies produced by B cells in milk could guide the development of vaccines that elicit protective mucosal antibody responses. METHODS: We isolated B cells from colostrum of an HIV-infected lactating woman with a detectable neutralization response in milk and recombinantly produced and characterized the resulting HIV-1 Envelope (Env)-specific monoclonal antibodies (mAbs). RESULTS: The identified HIV-1 Env-specific colostrum mAbs, CH07 and CH08, represent two of the first mucosally-derived anti-HIV antibodies yet to be reported. Colostrum mAb CH07 is a highly-autoreactive, weakly-neutralizing gp140-specific mAb that binds to linear epitopes in the gp120 C5 region and gp41 fusion domain. In contrast, colostrum mAb CH08 is a nonpolyreactive CD4-inducible (CD4i) gp120-specific mAb with moderate breadth of neutralization. CONCLUSIONS: These novel HIV-neutralizing mAbs isolated from a mucosal compartment provide insight into the ability of mucosal B cell populations to produce functional anti-HIV antibodies that may contribute to protection against virus acquisition at mucosal surfaces.
Alam, S. Munir
Fouda, Genevieve Giny
Haynes, Barton Ford
Kelsoe, Garnett H.
Moody, Michael Anthony
Permar, Sallie Robey
Pollara, Justin Joseph
Tomaras, Georgia Doris
Friedman, J; Alam, SM; Shen, X; Xia, S-M; Stewart, S; Anasti, K; Pollara, J; Fouda, GG; Yang, G; Kelsoe, G; Ferrari, G; Tomaras, GD; Haynes, BF; Liao, H-X; Moody, MA; Permar, SR
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