Barton Ford Haynes, MD

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Professor of Medicine
Research Professor of Global Health
Professor of Immunology
Director of the Human Vaccine Institute in the Department of Medicine
Department / Division:
Medicine / Medicine-HVI-Haynes
Address:
106 Research Drive
Msrbii 4090
Durham, NC 27710
Office Telephone:
(919) 684-5384
Training:
  • MD, Baylor University, 1973
Research Interests:
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 ce
Representative Publications:
  • 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, HX; Haynes, B; Geall, AJ; Barnett, SW. Potent immune responses in rhesus macaques induced by non-viral delivery of a self-amplifying RNA vaccine expressing HIV-1 envelope with a cationic nanoemulsion. Journal of Infectious Diseases. 2014;  Abstract
  • Bonsignori, M; Wiehe, K; Grimm, SK; Lynch, R; Yang, G; Kozink, DM; Perrin, F; Cooper, AJ; Hwang, KK; Chen, X; Liu, M; McKee, K; Parks, RJ; Eudailey, J; Wang, M; Clowse, M; Criscione-Schreiber, LG; Moody, MA; Ackerman, ME; Boyd, SD; Gao, F; Kelsoe, G; Verkoczy, L; Tomaras, GD; Liao, HX; Kepler, TB; Montefiori, DC; Mascola, JR; Haynes, BF. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. Journal of Clinical Investigation. 2014;124:1835-1843.  Abstract
  • Dennison, SM; Anasti, KM; Jaeger, FH; Stewart, SM; Pollara, J; Liu, P; Kunz, EL; Zhang, R; Vandergrift, N; Permar, S; Ferrari, G; Tomaras, GD; Bonsignori, M; Michael, NL; Kim, JH; Kaewkungwal, J; Nitayaphan, S; Pitisuttithum, P; Rerks-Ngarm, S; Liao, HX; Haynes, BF; Alam, SM. Vaccine-induced HIV-1 envelope gp120 constant region 1-specific antibodies expose a CD4-inducible epitope and block the interaction of HIV-1 gp140 with galactosylceramide. Journal of Virology. 2014;88:9406-9417.  Abstract
  • Fera, D; Schmidt, AG; Haynes, BF; Gao, F; Liao, HX; Kepler, TB; Harrison, SC. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains. Proceedings of the National Academy of Sciences of USA. 2014;111:10275-10280.  Abstract
  • 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, HX; Haynes, BF; Montefiori, DC; Ferrari, G; Tomaras, GD; Permar, SR. Infant HIV-1 gp120 vaccination elicits robust and durable anti-V1V2 IgG responses and only rare Envelope-specific IgA responses. Journal of Infectious Diseases. 2014;  Abstract
  • Gao, F; Bonsignori, M; Liao, HX; Kumar, A; Xia, SM; Lu, X; Cai, F; Hwang, KK; Song, H; Zhou, T; Lynch, RM; Alam, SM; Moody, MA; Ferrari, G; Berrong, M; Kelsoe, G; Shaw, GM; Hahn, BH; Montefiori, DC; Kamanga, G; Cohen, MS; Hraber, P; Kwong, PD; Korber, BT; Mascola, JR; Kepler, TB; Haynes, BF. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell. 2014;158:481-491.  Abstract
  • Giorgi, EE; Balachandran, H; Muldoon, M; Letvin, NL; Haynes, BF; Korber, BT; Santra, S. Cross-reactive potential of human T-lymphocyte responses in HIV-1 infection. Vaccine. 2014;32:3995-4000.  Abstract
  • Haynes, BF; Verkoczy, L. AIDS/HIV. Host controls of HIV neutralizing antibodies. Science. 2014;344:588-589.  Abstract
  • Haynes, BF; Verkoczy, L. Host controls of HIV neutralizing antibodies. Science. 2014;344:588-589.  
  • Haynes, BF; Verkoczy, L; Kelsoe, G. Redemption of autoreactive B cells. Proceedings of the National Academy of Sciences of USA. 2014;111:9022-9023.  Abstract
  • Holl, TM; Yang, G; Kuraoka, M; Verkoczy, L; Alam, SM; Moody, MA; Haynes, BF; Kelsoe, G. Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes. Journal of Immunology. 2014;192:3269-3279.  Abstract
  • Huang, J; Kang, BH; Pancera, M; Lee, JH; Tong, T; Feng, Y; Imamichi, H; Georgiev, IS; Chuang, GY; Druz, A; Doria-Rose, NA; Laub, L; Sliepen, K; van Gils, MJ; de la Peña, AT; Derking, R; Klasse, PJ; Migueles, SA; Bailer, RT; Alam, M; Pugach, P; Haynes, BF; Wyatt, RT; Sanders, RW; Binley, JM; Ward, AB; Mascola, JR; Kwong, PD; Connors, M. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature. 2014;515:138-142.  Abstract
  • Hwang, KK; Trama, AM; Kozink, DM; Chen, X; Wiehe, K; Cooper, AJ; Xia, SM; Wang, M; Marshall, DJ; Whitesides, J; Alam, M; Tomaras, GD; Allen, SL; Rai, KR; McKeating, J; Catera, R; Yan, XJ; Chu, CC; Kelsoe, G; Liao, HX; Chiorazzi, N; Haynes, BF. IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria. PLoS One. 2014;9:e90725.  Abstract
  • Kepler, TB; Liao, HX; 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, SS; Cohen, MS; Walter, E; Moody, MA; Wu, X; Altae-Tran, HR; Georgiev, IS; Kwong, PD; Boyd, SD; Fire, AZ; Mascola, JR; Haynes, BF. Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies. Cell Host and Microbe. 2014;16:304-313.  Abstract
  • Kepler, TB; Munshaw, S; Wiehe, K; Zhang, R; Yu, JS; Woods, CW; Denny, TN; Tomaras, GD; Alam, SM; Moody, MA; Kelsoe, G; Liao, HX; Haynes, BF. Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation. Frontiers in Immunology. 2014;5:170.  Abstract
  • Li, SS; Gilbert, PB; Tomaras, GD; Kijak, G; Ferrari, G; Thomas, R; Pyo, CW; Zolla-Pazner, S; Montefiori, D; Liao, HX; 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; Geraghty, DE. FCGR2C polymorphisms associate with HIV-1 vaccine protection in RV144 trial. Journal of Clinical Investigation. 2014;124:3879-3890.  Abstract
  • Liu, P; Williams, LD; Shen, X; Bonsignori, M; Vandergrift, NA; Overman, RG; Moody, MA; Liao, HX; Stieh, DJ; McCotter, KL; French, AL; Hope, TJ; Shattock, R; Haynes, BF; Tomaras, GD. Capacity for infectious HIV-1 virion capture differs by envelope antibody specificity. Journal of Virology. 2014;88:5165-5170.  Abstract
  • Madani, N; Princiotto, AM; Schön, A; LaLonde, J; Feng, Y; Freire, E; Park, J; Courter, JR; Jones, DM; Robinson, J; Liao, HX; Moody, MA; Permar, S; Haynes, B; Smith, AB; Wyatt, R; Sodroski, J. CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies. Journal of Virology. 2014;88:6542-6555.  Abstract
  • Moody, MA; Santra, S; Vandergrift, NA; Sutherland, LL; Gurley, TC; Drinker, MS; Allen, AA; Xia, SM; Meyerhoff, RR; Parks, R; Lloyd, KE; Easterhoff, D; Alam, SM; Liao, HX; Ward, BM; Ferrari, G; Montefiori, DC; Tomaras, GD; Seder, RA; Letvin, NL; Haynes, BF. Toll-like receptor 7/8 (TLR7/8) and TLR9 agonists cooperate to enhance HIV-1 envelope antibody responses in rhesus macaques. Journal of Virology. 2014;88:3329-3339.  Abstract
  • 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; Gillard, GO. Gene Deletions in Mycobacterium bovis BCG Stimulate Increased CD8+ T Cell Responses. Infection and Immunity. 2014;82:5317-5326.  Abstract
  • Pancera, M; Zhou, T; Druz, A; Georgiev, IS; Soto, C; Gorman, J; Huang, J; Acharya, P; Chuang, GY; Ofek, G; Stewart-Jones, GB; 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; Kwong, PD. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014;514:455-461.  Abstract
  • Pollara, J; Bonsignori, M; Moody, MA; Liu, P; Alam, SM; Hwang, KK; Gurley, TC; Kozink, DM; Armand, LC; Marshall, DJ; Whitesides, JF; Kaewkungwal, J; Nitayaphan, S; Pitisuttithum, P; Rerks-Ngarm, S; Robb, ML; O'Connell, RJ; Kim, JH; Michael, NL; Montefiori, DC; Tomaras, GD; Liao, HX; Haynes, BF; Ferrari, G. HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities. Journal of Virology. 2014;88:7715-7726.  Abstract
  • Reardon, PN; Sage, H; Dennison, SM; Martin, JW; Donald, BR; Alam, SM; Haynes, BF; Spicer, LD. Structure of an HIV-1-neutralizing antibody target, the lipid-bound gp41 envelope membrane proximal region trimer. Proceedings of the National Academy of Sciences of USA. 2014;111:1391-1396.  Abstract
  • Rudicell, RS; Kwon, YD; Ko, SY; Pegu, A; Louder, MK; Georgiev, IS; Wu, X; Zhu, J; Boyington, JC; Chen, X; Shi, W; Yang, ZY; Doria-Rose, NA; McKee, K; O'Dell, S; Schmidt, SD; Chuang, GY; Druz, A; Soto, C; Yang, Y; Zhang, B; Zhou, T; Todd, JP; 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; Nabel, GJ. Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo. Journal of Virology. 2014;88:12669-12682.  Abstract
  • 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; 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. 2014;  Abstract
  • 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; Korioth-Schmitz, B. Recombinant Mycobacterium bovis bacillus Calmette-Guerin vectors prime for strong cellular responses to simian immunodeficiency virus gag in rhesus macaques. Clinical and Vaccine Immunology. 2014;21:1385-1395.  Abstract
  • Tomaras, GD; Haynes, BF. Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates. Vaccines. 2014;2:15-35.  Abstract
  • Tomaras, GD; Haynes, BF. Lessons from babies: inducing HIV-1 broadly neutralizing antibodies. Nature Medicine. 2014;20:583-585.  Abstract
  • Trama, AM; Moody, MA; Alam, SM; Jaeger, FH; Lockwood, B; Parks, R; Lloyd, KE; Stolarchuk, C; Scearce, R; Foulger, A; Marshall, DJ; Whitesides, JF; Jeffries, TL; Wiehe, K; Morris, L; Lambson, B; Soderberg, K; Hwang, KK; Tomaras, GD; Vandergrift, N; Jackson, KJ; Roskin, KM; Boyd, SD; Kepler, TB; Liao, HX; Haynes, BF. HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria. Cell Host and Microbe. 2014;16:215-226.  Abstract
  • Veillette, M; Désormeaux, A; Medjahed, H; Gharsallah, N-E; Coutu, M; Baalwa, J; Guan, Y; Lewis, G; Ferrari, G; Hahn, BH; Haynes, BF; Robinson, JE; Kaufmann, DE; Bonsignori, M; Sodroski, J; Finzi, A. Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. Journal of Virology. 2014;88:2633-2644.  
  • Veillette, M; Désormeaux, A; Medjahed, H; Gharsallah, NE; Coutu, M; Baalwa, J; Guan, Y; Lewis, G; Ferrari, G; Hahn, BH; Haynes, BF; Robinson, JE; Kaufmann, DE; Bonsignori, M; Sodroski, J; Finzi, A. Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. Journal of Virology. 2014;88:2633-2644.  Abstract
  • Verkoczy, L; Kelsoe, G; Haynes, BF. HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine development. PLoS Pathogens. 2014;10:e1004073.  Abstract
  • Yates, NL; Liao, HX; Fong, Y; deCamp, A; Vandergrift, NA; Williams, WT; Alam, SM; Ferrari, G; Yang, ZY; Seaton, KE; Berman, PW; Alpert, MD; Evans, DT; O'Connell, RJ; Francis, D; Sinangil, F; Lee, C; Nitayaphan, S; Rerks-Ngarm, S; Kaewkungwal, J; Pitisuttithum, P; Tartaglia, J; Pinter, A; Zolla-Pazner, S; Gilbert, PB; Nabel, GJ; Michael, NL; Kim, JH; Montefiori, DC; Haynes, BF; Tomaras, GD. Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Science Translational Medicine. 2014;6:228ra39.  Abstract
  • Zhang, J; Alam, SM; Bouton-Verville, H; Chen, Y; Newman, A; Stewart, S; Jaeger, FH; Montefiori, DC; Dennison, SM; Haynes, BF; Verkoczy, L. Modulation of nonneutralizing HIV-1 gp41 responses by an MHC-restricted TH epitope overlapping those of membrane proximal external region broadly neutralizing antibodies. Journal of Immunology. 2014;192:1693-1706.  Abstract
  • Zhang, J; Alam, SM; Bouton-Verville, H; Chen, Y; Newman, A; Stewart, S; Jaeger, FH; Montefiori, DC; Dennison, SM; Haynes, BF; Verkoczy, L. Modulation of nonneutralizing HIV-1 gp41 responses by an MHC-restricted TH epitope overlapping those of membrane proximal external region broadly neutralizing antibodies. Journal of Immunology. 2014;192:1693-1706.  
  • Zolla-Pazner, S; deCamp, A; Gilbert, PB; Williams, C; Yates, NL; Williams, WT; Howington, R; Fong, Y; Morris, DE; Soderberg, KA; Irene, C; Reichman, C; Pinter, A; Parks, R; Pitisuttithum, P; Kaewkungwal, J; Rerks-Ngarm, S; Nitayaphan, S; Andrews, C; O'Connell, RJ; Yang, ZY; Nabel, GJ; Kim, JH; Michael, NL; Montefiori, DC; Liao, HX; Haynes, BF; Tomaras, GD. Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLoS One. 2014;9:e87572.  Abstract