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

McCurley, NP, Domi, A, Basu, R, Saunders, KO, LaBranche, CC, Montefiori, DC, Haynes, BF, and Robinson, HL. "HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site." PloS one 12, no. 10 (January 2017): e0177863-.

PMID
29020058
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Ramesh, A, Darko, S, Hua, A, Overman, G, Ransier, A, Francica, JR, Trama, A, Tomaras, GD, Haynes, BF, Douek, DC, and Kepler, TB. "Structure and Diversity of the Rhesus Macaque Immunoglobulin Loci through Multiple De Novo Genome Assemblies." Frontiers in immunology 8 (January 2017): 1407-.

PMID
29163486
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Luo, K, Liao, H-X, Zhang, R, Easterhoff, D, Wiehe, K, Gurley, TC, Armand, LC, Allen, AA, Von Holle, TA, Marshall, DJ, Whitesides, JF, Pritchett, J, Foulger, A, Hernandez, G, Parks, R, Lloyd, KE, Stolarchuk, C, Sawant, S, Peel, J, Yates, NL, Dunford, E, Arora, S, Wang, A, Bowman, CM, Sutherland, LL, Scearce, RM, Xia, S-M, Bonsignori, M, Pollara, J, Edwards, RW, Santra, S, Letvin, NL, Tartaglia, J, Francis, D, Sinangil, F, Lee, C, Kaewkungwal, J, Nitayaphan, S, Pitisuttithum, P, and Rerks-Ngarm, S et al. "Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques." JCI insight 1, no. 20 (December 8, 2016): e88522-.

PMID
27942585
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Astronomo, RD, Santra, S, Ballweber-Fleming, L, Westerberg, KG, Mach, L, Hensley-McBain, T, Sutherland, L, Mildenberg, B, Morton, G, Yates, NL, Mize, GJ, Pollara, J, Hladik, F, Ochsenbauer, C, Denny, TN, Warrier, R, Rerks-Ngarm, S, Pitisuttithum, P, Nitayapan, S, Kaewkungwal, J, Ferrari, G, Shaw, GM, Xia, S-M, Liao, H-X, Montefiori, DC, Tomaras, GD, Haynes, BF, and McElrath, JM. "Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection." Ebiomedicine 14 (December 2016): 97-111.

PMID
27919754
Full Text

Ferrari, G, Haynes, BF, Koenig, S, Nordstrom, JL, Margolis, DM, and Tomaras, GD. "Envelope-specific antibodies and antibody-derived molecules for treating and curing HIV infection." Nature Reviews. Drug Discovery 15, no. 12 (December 2016): 823-834. (Review)

PMID
27725635
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Bradley, T, Yang, G, Ilkayeva, O, Holl, TM, Zhang, R, Zhang, J, Santra, S, Fox, CB, Reed, SG, Parks, R, Bowman, CM, Bouton-Verville, H, Sutherland, LL, Scearce, RM, Vandergrift, N, Kepler, TB, Moody, MA, Liao, H-X, Alam, SM, McLendon, R, Everitt, JI, Newgard, CB, Verkoczy, L, Kelsoe, G, and Haynes, BF. "HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism." Journal of Immunology (Baltimore, Md. : 1950) 197, no. 12 (December 2016): 4663-4673.

PMID
27849170
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Raymond, DD, Stewart, SM, Lee, J, Ferdman, J, Bajic, G, Do, KT, Ernandes, MJ, Suphaphiphat, P, Settembre, EC, Dormitzer, PR, Del Giudice, G, Finco, O, Kang, TH, Ippolito, GC, Georgiou, G, Kepler, TB, Haynes, BF, Moody, MA, Liao, H-X, Schmidt, AG, and Harrison, SC. "Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain." Nature Medicine 22, no. 12 (December 2016): 1465-1469.

PMID
27820604
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Negri, D, Blasi, M, LaBranche, C, Parks, R, Balachandran, H, Lifton, M, Shen, X, Denny, T, Ferrari, G, Vescio, MF, Andersen, H, Montefiori, DC, Tomaras, GD, Liao, H-X, Santra, S, Haynes, BF, Klotman, ME, and Cara, A. "Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques." Molecular Therapy : the Journal of the American Society of Gene Therapy 24, no. 11 (November 2016): 2021-2032.

PMID
27455880
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Huang, J, Kang, BH, Ishida, E, Zhou, T, Griesman, T, Sheng, Z, Wu, F, Doria-Rose, NA, Zhang, B, McKee, K, O'Dell, S, Chuang, G-Y, Druz, A, Georgiev, IS, Schramm, CA, Zheng, A, Joyce, MG, Asokan, M, Ransier, A, Darko, S, Migueles, SA, Bailer, RT, Louder, MK, Alam, SM, Parks, R, Kelsoe, G, Von Holle, T, Haynes, BF, Douek, DC, Hirsch, V, Seaman, MS, Shapiro, L, Mascola, JR, Kwong, PD, and Connors, M. "Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth." Immunity 45, no. 5 (November 2016): 1108-1121.

PMID
27851912
Full Text

Negri, D, Blasi, M, LaBranche, C, Parks, R, Balachandran, H, Lifton, M, Shen, X, Denny, T, Ferrari, G, Vescio, MF, Andersen, H, Montefiori, DC, Tomaras, GD, Liao, H-X, Santra, S, Haynes, BF, Klotman, ME, and Cara, A. "Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques." MOLECULAR THERAPY 24, no. 11 (November 2016): 2021-2032.

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