Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
Repository Usage Stats
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.
Fluorescent Antibody Technique, Indirect
HIV Envelope Protein gp120
Published Version (Please cite this version)10.1371/journal.pone.0037648
More InfoShow full item record
Showing items related by title, author, creator, and subject.
McLellan, JS; Pancera, M; Carrico, C; Gorman, J; Julien, J-P; Khayat, R; Louder, R; Pejchal, R; Sastry, M; Dai, K; O'Dell, S; Patel, N; Shahzad-ul-Hussan, S; Yang, Y; Zhang, B; Zhou, T; Zhu, J; Boyington, JC; Chuang, G-Y; Diwanji, D; Georgiev, I; Kwon, YD; Lee, D; Louder, MK; Moquin, S; Schmidt, SD; Yang, Z-Y; Bonsignori, Mattia; Crump, John Andrew; Kapiga, SH; Sam, NE; Haynes, BF; Burton, DR; Koff, WC; Walker, LM; Phogat, S; Wyatt, R; Orwenyo, J; Wang, L-X; Arthos, J; Bewley, CA; Mascola, JR; Nabel, GJ; Schief, WR; Ward, AB; Wilson, IA; Kwong, PD (Nature, 2011-11-23)Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence ...
Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1. Pollara, J; McGuire, E; Fouda, GG; Rountree, W; Eudailey, J; Overman, RG; Seaton, KE; Deal, A; Edwards, RW; Tegha, G; Kamwendo, D; Kumwenda, J; Nelson, JA; Liao, HX; Brinkley, C; Denny, TN; Ochsenbauer, C; Ellington, S; King, CC; Jamieson, DJ; van der Horst, C; Kourtis, AP; Tomaras, GD; Ferrari, G; Permar, SR (J Virol, 2015-10)UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants ...
HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies. Fouda, GG; Yates, NL; Pollara, Justin Joseph; Shen, X; Overman, GR; Mahlokozera, T; Wilks, AB; Kang, HH; Salazar-Gonzalez, JF; Salazar, MG; Kalilani, L; Meshnick, SR; Hahn, BH; Shaw, GM; Lovingood, RV; Denny, Thomas Norton; Haynes, B; Letvin, NL; Ferrari, Guido; Montefiori, DC; Tomaras, GD; Permar, SR; Center for HIV/AIDS Vaccine Immunology (J Virol, 2011-09)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 ...