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, B. "E-103 The pathway to HIV vaccine development." January 2016.

Full Text

Schmidt, AG, Do, KT, McCarthy, KR, Kepler, TB, Liao, H-X, Moody, MA, Haynes, BF, and Harrison, SC. "Immunogenic Stimulus for Germline Precursors of Antibodies that Engage the Influenza Hemagglutinin Receptor-Binding Site." Cell reports 13, no. 12 (December 16, 2015): 2842-2850.

PMID
26711348
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Sung, JAM, Pickeral, J, Liu, L, Stanfield-Oakley, SA, Lam, C-YK, Garrido, C, Pollara, J, LaBranche, C, Bonsignori, M, Moody, MA, Yang, Y, Parks, R, Archin, N, Allard, B, Kirchherr, J, Kuruc, JD, Gay, CL, Cohen, MS, Ochsenbauer, C, Soderberg, K, Liao, H-X, Montefiori, D, Moore, P, Johnson, S, Koenig, S, Haynes, BF, Nordstrom, JL, Margolis, DM, and Ferrari, G. "Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells." The Journal of clinical investigation 125, no. 11 (November 2015): 4077-4090.

PMID
26413868
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Hraber, P, Korber, B, Wagh, K, Giorgi, EE, Bhattacharya, T, Gnanakaran, S, Lapedes, AS, Learn, GH, Kreider, EF, Li, Y, Shaw, GM, Hahn, BH, Montefiori, DC, Alam, SM, Bonsignori, M, Moody, MA, Liao, H-X, Gao, F, and Haynes, BF. "Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants." Viruses 7, no. 10 (October 21, 2015): 5443-5475.

PMID
26506369
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Doria-Rose, NA, Bhiman, JN, Roark, RS, Schramm, CA, Gorman, J, Chuang, G-Y, Pancera, M, Cale, EM, Ernandes, MJ, Louder, MK, Asokan, M, Bailer, RT, Druz, A, Fraschilla, IR, Garrett, NJ, Jarosinski, M, Lynch, RM, McKee, K, O'Dell, S, Pegu, A, Schmidt, SD, Staupe, RP, Sutton, MS, Wang, K, Wibmer, CK, Haynes, BF, Abdool-Karim, S, Shapiro, L, Kwong, PD, Moore, PL, Morris, L, and Mascola, JR. "New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency." Journal of virology 90, no. 1 (October 14, 2015): 76-91.

PMID
26468542
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Corey, L, Gilbert, PB, Tomaras, GD, Haynes, BF, Pantaleo, G, and Fauci, AS. "Immune correlates of vaccine protection against HIV-1 acquisition." Science translational medicine 7, no. 310 (October 2015): 310rv7-. (Review)

PMID
26491081
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Moody, MA, Gao, F, Gurley, TC, Amos, JD, Kumar, A, Hora, B, Marshall, DJ, Whitesides, JF, Xia, S-M, Parks, R, Lloyd, KE, Hwang, K-K, Lu, X, Bonsignori, M, Finzi, A, Vandergrift, NA, Alam, SM, Ferrari, G, Shen, X, Tomaras, GD, Kamanga, G, Cohen, MS, Sam, NE, Kapiga, S, Gray, ES, Tumba, NL, Morris, L, Zolla-Pazner, S, Gorny, MK, Mascola, JR, Hahn, BH, Shaw, GM, Sodroski, JG, Liao, H-X, Montefiori, DC, Hraber, PT, Korber, BT, and Haynes, BF. "Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses." Cell host & microbe 18, no. 3 (September 2015): 354-362.

PMID
26355218
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Santra, S, Tomaras, GD, Warrier, R, Nicely, NI, Liao, H-X, Pollara, J, Liu, P, Alam, SM, Zhang, R, Cocklin, SL, Shen, X, Duffy, R, Xia, S-M, Schutte, RJ, Pemble Iv, CW, Dennison, SM, Li, H, Chao, A, Vidnovic, K, Evans, A, Klein, K, Kumar, A, Robinson, J, Landucci, G, Forthal, DN, Montefiori, DC, Kaewkungwal, J, Nitayaphan, S, Pitisuttithum, P, Rerks-Ngarm, S, Robb, ML, Michael, NL, Kim, JH, Soderberg, KA, Giorgi, EE, Blair, L, Korber, BT, Moog, C, Shattock, RJ, Letvin, NL, and Schmitz, JE et al. "Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques." PLoS pathogens 11, no. 8 (August 3, 2015): e1005042-.

PMID
26237403
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Wieczorek, L, Krebs, SJ, Kalyanaraman, V, Whitney, S, Tovanabutra, S, Moscoso, CG, Sanders-Buell, E, Williams, C, Slike, B, Molnar, S, Dussupt, V, Alam, SM, Chenine, A-L, Tong, T, Hill, EL, Liao, H-X, Hoelscher, M, Maboko, L, Zolla-Pazner, S, Haynes, BF, Pensiero, M, McCutchan, F, Malek-Salehi, S, Cheng, RH, Robb, ML, VanCott, T, Michael, NL, Marovich, MA, Alving, CR, Matyas, GR, Rao, M, and Polonis, VR. "Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research." Journal of virology 89, no. 15 (August 2015): 7478-7493.

PMID
25972551
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Gombos, RB, Kolodkin-Gal, D, Eslamizar, L, Owuor, JO, Mazzola, E, Gonzalez, AM, Korioth-Schmitz, B, Gelman, RS, Montefiori, DC, Haynes, BF, and Schmitz, JE. "Inhibitory Effect of Individual or Combinations of Broadly Neutralizing Antibodies and Antiviral Reagents against Cell-Free and Cell-to-Cell HIV-1 Transmission." Journal of virology 89, no. 15 (August 2015): 7813-7828.

PMID
25995259
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