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

Madani, N, Princiotto, AM, Easterhoff, D, Bradley, T, Luo, K, Williams, WB, Liao, H-X, Moody, MA, Phad, GE, Vázquez Bernat, N, Melillo, B, Santra, S, Smith, AB, Karlsson Hedestam, GB, Haynes, B, and Sodroski, J. "Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds." Journal of Virology 90, no. 10 (May 2016): 5031-5046.

PMID
26962221
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Zhang, R, Verkoczy, L, Wiehe, K, Munir Alam, S, Nicely, NI, Santra, S, Bradley, T, Pemble, CW, Zhang, J, Gao, F, Montefiori, DC, Bouton-Verville, H, Kelsoe, G, Larimore, K, Greenberg, PD, Parks, R, Foulger, A, Peel, JN, Luo, K, Lu, X, Trama, AM, Vandergrift, N, Tomaras, GD, Kepler, TB, Moody, MA, Liao, H-X, and Haynes, BF. "Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages." Science translational medicine 8, no. 336 (April 2016): 336ra62-.

PMID
27122615
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Bonsignori, M, Zhou, T, Sheng, Z, Chen, L, Gao, F, Joyce, MG, Ozorowski, G, Chuang, G-Y, Schramm, CA, Wiehe, K, Alam, SM, Bradley, T, Gladden, MA, Hwang, K-K, Iyengar, S, Kumar, A, Lu, X, Luo, K, Mangiapani, MC, Parks, RJ, Song, H, Acharya, P, Bailer, RT, Cao, A, Druz, A, Georgiev, IS, Kwon, YD, Louder, MK, Zhang, B, Zheng, A, Hill, BJ, Kong, R, Soto, C, NISC Comparative Sequencing Program, , Mullikin, JC, Douek, DC, Montefiori, DC, Moody, MA, Shaw, GM, Hahn, BH, Kelsoe, G, and Hraber, PT et al. "Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody." Cell 165, no. 2 (April 2016): 449-463.

PMID
26949186
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Jeffries, TL, Sacha, CR, Pollara, J, Himes, J, Jaeger, FH, Dennison, SM, McGuire, E, Kunz, E, Eudailey, JA, Trama, AM, LaBranche, C, Fouda, GG, Wiehe, K, Montefiori, DC, Haynes, BF, Liao, H-X, Ferrari, G, Alam, SM, Moody, MA, and Permar, SR. "The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells." Mucosal Immunology 9, no. 2 (March 2016): 414-427.

PMID
26242599
Full Text

Haynes, BF, Shaw, GM, Korber, B, Kelsoe, G, Sodroski, J, Hahn, BH, Borrow, P, and McMichael, AJ. "HIV-Host Interactions: Implications for Vaccine Design." Cell host & microbe 19, no. 3 (March 2016): 292-303. (Review)

PMID
26922989
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Wang, Y, Kapoor, P, Parks, R, Silva-Sanchez, A, Alam, SM, Verkoczy, L, Liao, H-X, Zhuang, Y, Burrows, P, Levinson, M, Elgavish, A, Cui, X, Haynes, BF, and Schroeder, H. "HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence." Immunogenetics 68, no. 2 (February 2016): 145-155.

PMID
26687685
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Gorman, J, Soto, C, Yang, MM, Davenport, TM, Guttman, M, Bailer, RT, Chambers, M, Chuang, G-Y, DeKosky, BJ, Doria-Rose, NA, Druz, A, Ernandes, MJ, Georgiev, IS, Jarosinski, MC, Joyce, MG, Lemmin, TM, Leung, S, Louder, MK, McDaniel, JR, Narpala, S, Pancera, M, Stuckey, J, Wu, X, Yang, Y, Zhang, B, Zhou, T, NISC Comparative Sequencing Program, , Mullikin, JC, Baxa, U, Georgiou, G, McDermott, AB, Bonsignori, M, Haynes, BF, Moore, PL, Morris, L, Lee, KK, Shapiro, L, Mascola, JR, and Kwong, PD. "Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design." Nature structural & molecular biology 23, no. 1 (January 2016): 81-90.

PMID
26689967
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Bradley, T, Fera, D, Bhiman, J, Eslamizar, L, Lu, X, Anasti, K, Zhang, R, Sutherland, LL, Scearce, RM, Bowman, CM, Stolarchuk, C, Lloyd, KE, Parks, R, Eaton, A, Foulger, A, Nie, X, Karim, SSA, Barnett, S, Kelsoe, G, Kepler, TB, Alam, SM, Montefiori, DC, Moody, MA, Liao, H-X, Morris, L, Santra, S, Harrison, SC, and Haynes, BF. "Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site." Cell reports 14, no. 1 (January 2016): 43-54.

PMID
26725118
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Soto, C, Ofek, G, Joyce, MG, Zhang, B, McKee, K, Longo, NS, Yang, Y, Huang, J, Parks, R, Eudailey, J, Lloyd, KE, Alam, SM, Haynes, BF, NISC Comparative Sequencing Program, , Mullikin, JC, Connors, M, Mascola, JR, Shapiro, L, and Kwong, PD. "Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8." PloS one 11, no. 6 (January 2016): e0157409-.

PMID
27299673
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Zambonelli, C, Dey, AK, Hilt, S, Stephenson, S, Go, EP, Clark, DF, Wininger, M, Labranche, C, Montefiori, D, Liao, H-X, Swanstrom, RI, Desaire, H, Haynes, BF, Carfi, A, and Barnett, SW. "Generation and Characterization of a Bivalent HIV-1 Subtype C gp120 Protein Boost for Proof-of-Concept HIV Vaccine Efficacy Trials in Southern Africa." PloS one 11, no. 7 (January 2016): e0157391-.

PMID
27442017
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