Barton Ford Haynes, MD

Professor of Medicine
Frederic M. Hanes Professor of Medicine
Director of the Human Vaccine Institute in the Department of Medicine
Research Professor of Global Health
Professor of Immunology
Member of the Duke Cancer Institute
Member of the Duke Human Vaccine Institute
Campus mail 106 Research Drive, MSRBII 4090, Durham, NC 27710
Phone (919) 684-5384
Email address hayne002@mc.duke.edu

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 development of an HIV vaccine. The lab has developed a novel approach to define the B cell repertories in AHI in order to find neutralizing antibodies against the virus. This approach uses linear Immunoglobulin (Ig) heavy and light chain gene expression cassettes to express Ig V(H) and V(L) genes isolated from sorted single B cells as IgG1 antibody without a cloning step. This strategy was used to characterize the Ig repertoire of plasma cells/plasmablasts in AHI and to produce recombinant influenza mAbs from sorted single human plasmablasts after influenza vaccination.

The lab is also studying the earliest effect HIV-1 has on B cells. Analyzing blood and gut-associated lymphoid tissues (GALT) during acute HIV infection, they have found that as early as 17 days after transmission HIV-1 induces B cell class switching and 47 days after transmission, HIV-1 causes considerable damage to GALT germinal centers. They found that in AHI, GALT memory B cells induce polyclonal B cell activation due to the presence of HIV-1-specific, influenza-specific, and autoreactive antibodies. The team concluded from this study that early induction of polyclonal B cell differentiation, along with follicular damage and germinal center loss, may explain why HIV-1 induced antibody responses decline rapidly during acute HIV infection and why plasma antibody responses are delayed.

The lab is also looking at ways of generating long-lived memory B cell responses to HIV infection, another major hurdle in the development of a successful HIV-1 vaccine. The lab has found that in HIV-1 gp120 envelope vaccination and chronic HIV-1 infection, HIV-1 envelope induces predominantly short-lived memory B cell-dependent plasma antibodies.

Immunogen Design

To overcome the high level of genetic diversity in HIV-1 envelope genes, the Haynes lab is developing strategies to induce antibodies that cross-react with multiple strains of HIV. The lab has designed immunogens based on transmitted founder Envs and mosaic consensus Envs in collaboration with Dr. Bette Korber at Los Alamos National Laboratory. These immunogens are designed to induce antibodies that cross-react with a multiple subtype Env glycoproteins. The goal is to determine if cross-reactive mAbs to highly conserved epitopes in HIV-1 envelope glycoproteins can be induced. The team recently characterized a panel of ten mAbs that reacted with varying breadth to subtypes A, B, C, D, F, G, CRF01_AE, and a highly divergent SIVcpzUS Env protein. Two of the mAbs cross-reacted with all tested Env proteins, including SIVcpzUS Env and bound Env proteins with high affinity.

Mucosal Immune Responses in TB and Influenza

The Haynes lab is helping to develop novel approaches to TB vaccine development. The current therapeutic vaccine for TB, called BCG, may prevent complications from TB in children, but offers little protection against infection and disease in adults. The lab is focused on using live attenuated Mycobacterium tuberculosis mutants as vaccine candidates and is currently evaluating this approach in non-human primate studies. As part of the DHVI Influenza program, they are studying the B cell response to influenza in order to generate a “universal” flu vaccine. They are currently trying to express more highly conserved influenza antigens in recombinant vesicular stomatitis virus (rVSV) vectors in order to elicit robust T cell and antibody responses to those antigens.

Education and Training

  • M.D., Baylor University, 1973

Publications

Haynes, BF, Harden, EA, Telen, MJ, Hemler, ME, Strominger, JL, Palker, TJ, Scearce, RM, and Eisenbarth, GS. "Differentiation of human T lymphocytes. I. Acquisition of a novel human cell surface protein (p80) during normal intrathymic T cell maturation." Journal of Immunology (Baltimore, Md. : 1950) 131, no. 3 (September 1983): 1195-1200.

PMID
6224850
Scholars@Duke

Stevenson, HC, Miller, PJ, Waxdal, MJ, Haynes, BF, Thomas, CA, and Fauci, AS. "Interaction of pokeweed mitogen with monocytes in the activation of human lymphocytes." Immunology 49, no. 4 (August 1983): 633-640.

PMID
6347876
Scholars@Duke

Gallo, RC, Kalyanaraman, VS, Sarngadharan, MG, Sliski, A, Vonderheid, EC, Maeda, M, Nakao, Y, Yamada, K, Ito, Y, Gutensohn, N, Murphy, S, Bunn, PA, Catovsky, D, Greaves, MF, Blayney, DW, Blattner, W, Jarrett, WF, zur Hausen, H, Seligmann, M, Brouet, JC, Haynes, BF, Jegasothy, BV, Jaffe, E, Cossman, J, Broder, S, Fisher, RI, Golde, DW, and Robert-Guroff, M. "Association of the human type C retrovirus with a subset of adult T-cell cancers." Cancer Res 43, no. 8 (August 1983): 3892-3899.

PMID
6602653
Scholars@Duke

Haynes, BF, Harden, EA, Olanow, CW, Eisenbarth, GS, Wechsler, AS, Hensley, LL, and Roses, AD. "Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis: selective effect on T-cells in patients with thymic atrophy." Journal of Immunology (Baltimore, Md. : 1950) 131, no. 2 (August 1983): 773-777.

PMID
6408188
Scholars@Duke

Mann, DL, Haynes, BF, Thomas, C, Cole, D, Fauci, AS, and Poplack, DG. "Heterogeneity of acute lymphocytic leukemia cell surface markers as detected by monoclonal antibodies." Journal of the National Cancer Institute 71, no. 1 (July 1983): 11-17.

PMID
6602900
Scholars@Duke

Telen, MJ, Eisenbarth, GS, and Haynes, BF. "Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene." J Clin Invest 71, no. 6 (June 1983): 1878-1886.

PMID
6863545
Scholars@Duke

Dowell, BL, Gore, I, McCormick, GM, Haynes, BF, and Metzgar, RS. "A monoclonal antibody reactive with a second epitope of the 67,000-dalton human T cell antigen." Hum Immunol 7, no. 2 (June 1983): 95-104.

PMID
6190792
Scholars@Duke

Francke, U, Foellmer, BE, and Haynes, BF. "Chromosome mapping of human cell surface molecules: monoclonal anti-human lymphocyte antibodies 4F2, A3D8, and A1G3 define antigens controlled by different regions of chromosome 11." Somatic Cell Genet 9, no. 3 (May 1983): 333-344.

PMID
6190235
Scholars@Duke

Reitz, MS, Popovic, M, Haynes, BF, Clark, SC, and Gallo, RC. "Relatedness by nucleic acid hybridization of new isolates of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of provirus in uncultured leukemic blood cells." Virology 126, no. 2 (April 1983): 688-672.

PMID
6602415
Full Text

Haynes, BF, Miller, SE, Palker, TJ, Moore, JO, Dunn, PH, Bolognesi, DP, and Metzgar, RS. "Identification of human T cell leukemia virus in a Japanese patient with adult T cell leukemia and cutaneous lymphomatous vasculitis." Proceedings of the National Academy of Sciences of the United States of America 80, no. 7 (April 1983): 2054-2058.

PMID
6601276
Full Text

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