Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum.
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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
Publication InfoAlam, S Munir; Anasti, Kara; Ferrari, Guido; Fouda, Genevieve; Friedman, J; Haynes, Barton Ford; ... Yang, G (2012). Isolation of HIV-1-neutralizing mucosal monoclonal antibodies from human colostrum. PLoS One, 7(5). pp. e37648. 10.1371/journal.pone.0037648. Retrieved from https://hdl.handle.net/10161/10587.
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Professor in Medicine
Research Interests. The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Associate Professor of Surgery
The activities of the Ferrari Laboratory are based on both independent basic research and immune monitoring studies. The research revolves around three main areas of interest: class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity (ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation along with many other productive collaborations wi
Associate Professor in Pediatrics
Dr Fouda's research interest is in understanding infant immune responses in the setting of infection and vaccination. Her current work focuses on HIV mother to child transmission.
Frederic M. Hanes Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
James B. Duke Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
Professor of Pediatrics
Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS to characterize the virus-specific immune responses and virus evolution in breast milk and develop a maternal vaccine regimen for protection against breast milk transmission of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific immune responses and virus evolution in vertically-transmitting an
Assistant Professor in Surgery
Professor in Surgery
Research in the Tomaras Laboratory in the Duke Human Vaccine Institute and Departments of Surgery, Immunology, and Molecular Genetics and Microbiology at Duke University Medical Center, focuses on the identification of immune correlates of protection for preventative vaccines and identification of the mechanisms responsible for potent inhibition of human pathogens.
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Arthos, J; Bewley, CA; Bonsignori, Mattia; Boyington, JC; Burton, DR; Carrico, C; Chuang, G-Y; ... (47 authors) (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 diversity ...
Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1. Brinkley, C; Deal, A; Denny, Thomas Norton; Edwards, RW; Ellington, S; Eudailey, Josh; Ferrari, Guido; ... (25 authors) (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. Center for HIV/AIDS Vaccine Immunology; Denny, Thomas Norton; Ferrari, Guido; Fouda, Genevieve; Hahn, Beatrice H; Haynes, Barton Ford; Kalilani, L; ... (23 authors) (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 ...