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Barton Ford Haynes, MD

Frederic M. Hanes Professor of Medicine
Campus Mail: 106 Research Drive, MSRBII 4090, Durham, NC 27710
Phone: (919) 684-5384
Email: 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

Selected Publications

Xu, H, Schmidt, AG, O'Donnell, T, Therkelsen, MD, Kepler, TB, Moody, MA, Haynes, BF, Liao, H-X, Harrison, SC, and Shaw, DE. "Key mutations stabilize antigen-binding conformation during affinity maturation of a broadly neutralizing influenza antibody lineage." Proteins 83, no. 4 (April 2015): 771-780.

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Bogers, WM, Oostermeijer, H, Mooij, P, Koopman, G, Verschoor, EJ, Davis, D, Ulmer, JB, Brito, LA, Cu, Y, Banerjee, K, Otten, GR, Burke, B, Dey, A, Heeney, JL, Shen, X, Tomaras, GD, Labranche, C, Montefiori, DC, Liao, H-X, Haynes, B, Geall, AJ, and Barnett, SW. "Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion." The Journal of infectious diseases 211, no. 6 (March 2015): 947-955.

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Sacha, CR, Vandergrift, N, Jeffries, TL, McGuire, E, Fouda, GG, Liebl, B, Marshall, DJ, Gurley, TC, Stiegel, L, Whitesides, JF, Friedman, J, Badiabo, A, Foulger, A, Yates, NL, Tomaras, GD, Kepler, TB, Liao, HX, Haynes, BF, Moody, MA, and Permar, SR. "Restricted isotype, distinct variable gene usage, and high rate of gp120 specificity of HIV-1 envelope-specific B cells in colostrum compared with those in blood of HIV-1-infected, lactating African women." Mucosal immunology 8, no. 2 (March 2015): 316-326.

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Fouda, GG, Cunningham, CK, McFarland, EJ, Borkowsky, W, Muresan, P, Pollara, J, Song, LY, Liebl, BE, Whitaker, K, Shen, X, Vandergrift, NA, Overman, RG, Yates, NL, Moody, MA, Fry, C, Kim, JH, Michael, NL, Robb, M, Pitisuttithum, P, Kaewkungwal, J, Nitayaphan, S, Rerks-Ngarm, S, Liao, H-X, Haynes, BF, Montefiori, DC, Ferrari, G, Tomaras, GD, and Permar, SR. "Infant HIV type 1 gp120 vaccination elicits robust and durable anti-V1V2 immunoglobulin G responses and only rare envelope-specific immunoglobulin A responses." The Journal of infectious diseases 211, no. 4 (February 2015): 508-517.

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Asmal, M, Luedemann, C, Lavine, CL, Mach, LV, Balachandran, H, Brinkley, C, Denny, TN, Lewis, MG, Anderson, H, Pal, R, Sok, D, Le, K, Pauthner, M, Hahn, BH, Shaw, GM, Seaman, MS, Letvin, NL, Burton, DR, Sodroski, JG, Haynes, BF, and Santra, S. "Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes." Virology 475 (January 2015): 37-45.

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Liu, M, Yang, G, Wiehe, K, Nicely, NI, Vandergrift, NA, Rountree, W, Bonsignori, M, Alam, SM, Gao, J, Haynes, BF, and Kelsoe, G. "Polyreactivity and autoreactivity among HIV-1 antibodies." Journal of virology 89, no. 1 (January 2015): 784-798.

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Wiehe, K, Easterhoff, D, Luo, K, Nicely, NI, Bradley, T, Jaeger, FH, Dennison, SM, Zhang, R, Lloyd, KE, Stolarchuk, C, Parks, R, Sutherland, LL, Scearce, RM, Morris, L, Kaewkungwal, J, Nitayaphan, S, Pitisuttithum, P, Rerks-Ngarm, S, Sinangil, F, Phogat, S, Michael, NL, Kim, JH, Kelsoe, G, Montefiori, DC, Tomaras, GD, Bonsignori, M, Santra, S, Kepler, TB, Alam, SM, Moody, MA, Liao, H-X, and Haynes, BF. "Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved." Immunity 41, no. 6 (December 2014): 909-918.

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Panas, MW, Sixsmith, JD, White, K, Korioth-Schmitz, B, Shields, ST, Moy, BT, Lee, S, Schmitz, JE, Jacobs, WR, Porcelli, SA, Haynes, BF, Letvin, NL, and Gillard, GO. "Gene deletions in Mycobacterium bovis BCG stimulate increased CD8+ T cell responses." Infection and immunity 82, no. 12 (December 2014): 5317-5326.

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Huang, J, Kang, BH, Pancera, M, Lee, JH, Tong, T, Feng, Y, Imamichi, H, Georgiev, IS, Chuang, G-Y, Druz, A, Doria-Rose, NA, Laub, L, Sliepen, K, van Gils, MJ, de la Peña, AT, Derking, R, Klasse, P-J, Migueles, SA, Bailer, RT, Alam, M, Pugach, P, Haynes, BF, Wyatt, RT, Sanders, RW, Binley, JM, Ward, AB, Mascola, JR, Kwong, PD, and Connors, M. "Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface." Nature 515, no. 7525 (November 2014): 138-142.

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Rudicell, RS, Kwon, YD, Ko, S-Y, Pegu, A, Louder, MK, Georgiev, IS, Wu, X, Zhu, J, Boyington, JC, Chen, X, Shi, W, Yang, Z-Y, Doria-Rose, NA, McKee, K, O'Dell, S, Schmidt, SD, Chuang, G-Y, Druz, A, Soto, C, Yang, Y, Zhang, B, Zhou, T, Todd, J-P, Lloyd, KE, Eudailey, J, Roberts, KE, Donald, BR, Bailer, RT, Ledgerwood, J, Mullikin, JC, Shapiro, L, Koup, RA, Graham, BS, Nason, MC, Connors, M, Haynes, BF, Rao, SS, Roederer, M, Kwong, PD, Mascola, JR, and Nabel, GJ. "Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo." Journal of virology 88, no. 21 (November 2014): 12669-12682.

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Pancera, M, Zhou, T, Druz, A, Georgiev, IS, Soto, C, Gorman, J, Huang, J, Acharya, P, Chuang, G-Y, Ofek, G, Stewart-Jones, GBE, Stuckey, J, Bailer, RT, Joyce, MG, Louder, MK, Tumba, N, Yang, Y, Zhang, B, Cohen, MS, Haynes, BF, Mascola, JR, Morris, L, Munro, JB, Blanchard, SC, Mothes, W, Connors, M, and Kwong, PD. "Structure and immune recognition of trimeric pre-fusion HIV-1 Env." Nature 514, no. 7523 (October 8, 2014): 455-461.

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Moody, MA, Easterhoff, D, Gurley, TC, Whitesides, JF, Marshall, DJ, Foulger, A, Lloyd, KE, Parks, R, Pollara, J, Duffy, R, Shen, S, Kim, JH, Michael, NL, Robb, ML, O'Connell, RJ, Vasan, S, Excler, JL, Rerks-Ngarm, S, Kaewkungwal, J, Pitisuttithum, P, Nitayaphan, S, Sinangil, F, Francis, D, Lee, C, Kepler, TB, Alam, SM, Ferrari, G, Montefiori, DC, Liao, HX, Tomaras, GD, and Haynes, BF. "Induction of Antibodies with Long Variable Heavy Third Complementarity Determining Regions by Repetitive Boosting with AIDSVAX® B/E in RV144 Vaccinees." October 2014.

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Sixsmith, JD, Panas, MW, Lee, S, Gillard, GO, White, K, Lifton, MA, Balachandran, H, Mach, L, Miller, JP, Lavine, C, DeMarco, CT, Tomaras, GD, Gee, C, Porcelli, SA, Larsen, MH, Frothingham, R, Schmitz, JE, Jacobs, WR, Haynes, BF, Letvin, NL, and Korioth-Schmitz, B. "Recombinant Mycobacterium bovis bacillus Calmette-Guérin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques." Clinical and vaccine immunology : CVI 21, no. 10 (October 2014): 1385-1395.

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Li, SS, Gilbert, PB, Tomaras, GD, Kijak, G, Ferrari, G, Thomas, R, Pyo, C-W, Zolla-Pazner, S, Montefiori, D, Liao, H-X, Nabel, G, Pinter, A, Evans, DT, Gottardo, R, Dai, JY, Janes, H, Morris, D, Fong, Y, Edlefsen, PT, Li, F, Frahm, N, Alpert, MD, Prentice, H, Rerks-Ngarm, S, Pitisuttithum, P, Kaewkungwal, J, Nitayaphan, S, Robb, ML, O'Connell, RJ, Haynes, BF, Michael, NL, Kim, JH, McElrath, MJ, and Geraghty, DE. "FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial." The Journal of clinical investigation 124, no. 9 (September 2014): 3879-3890.

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Kepler, TB, Liao, H-X, Alam, SM, Bhaskarabhatla, R, Zhang, R, Yandava, C, Stewart, S, Anasti, K, Kelsoe, G, Parks, R, Lloyd, KE, Stolarchuk, C, Pritchett, J, Solomon, E, Friberg, E, Morris, L, Karim, SSA, Cohen, MS, Walter, E, Moody, MA, Wu, X, Altae-Tran, HR, Georgiev, IS, Kwong, PD, Boyd, SD, Fire, AZ, Mascola, JR, and Haynes, BF. "Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies." Cell host & microbe 16, no. 3 (September 2014): 304-313.

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