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, K-K, Tomaras, GD, Vandergrift, N, Jackson, KJL, Roskin, KM, Boyd, SD, Kepler, TB, Liao, H-X, and Haynes, BF. "HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria." Cell host & microbe 16, no. 2 (August 2014): 215-226.
Barton Ford Haynes, MD
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.
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
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, H-X, Haynes, BF, and 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 88, no. 16 (August 2014): 9406-9417.
Gao, F, Bonsignori, M, Liao, H-X, Kumar, A, Xia, S-M, Lu, X, Cai, F, Hwang, K-K, 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, and Haynes, BF. "Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies." Cell 158, no. 3 (July 24, 2014): 481-491.
Fera, D, Schmidt, AG, Haynes, BF, Gao, F, Liao, H-X, Kepler, TB, and 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 the United States of America 111, no. 28 (July 2014): 10275-10280.
Pollara, J, Bonsignori, M, Moody, MA, Liu, P, Alam, SM, Hwang, K-K, 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, H-X, Haynes, BF, and Ferrari, G. "HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities." Journal of virology 88, no. 14 (July 2014): 7715-7726.
Haynes, BF, Verkoczy, L, and Kelsoe, G. "Redemption of autoreactive B cells." Proceedings of the National Academy of Sciences of the United States of America 111, no. 25 (June 11, 2014): 9022-9023.
Madani, N, Princiotto, AM, Schön, A, LaLonde, J, Feng, Y, Freire, E, Park, J, Courter, JR, Jones, DM, Robinson, J, Liao, H-X, Moody, MA, Permar, S, Haynes, B, Smith, AB, Wyatt, R, and Sodroski, J. "CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies." Journal of virology 88, no. 12 (June 2014): 6542-6555.
Giorgi, EE, Balachandran, H, Muldoon, M, Letvin, NL, Haynes, BF, Korber, BT, and Santra, S. "Cross-reactive potential of human T-lymphocyte responses in HIV-1 infection." Vaccine 32, no. 31 (June 2014): 3995-4000.
Tomaras, GD, and Haynes, BF. "Lessons from babies: inducing HIV-1 broadly neutralizing antibodies." Nature medicine 20, no. 6 (June 2014): 583-585.
Verkoczy, L, Kelsoe, G, and Haynes, BF. "HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine development." PLoS pathogens 10, no. 5 (May 22, 2014): e1004073-.
Haynes, BF, and Verkoczy, L. "AIDS/HIV. Host controls of HIV neutralizing antibodies." Science (New York, N.Y.) 344, no. 6184 (May 2014): 588-589.
Liu, P, Williams, LD, Shen, X, Bonsignori, M, Vandergrift, NA, Overman, RG, Moody, MA, Liao, H-X, Stieh, DJ, McCotter, KL, French, AL, Hope, TJ, Shattock, R, Haynes, BF, and Tomaras, GD. "Capacity for infectious HIV-1 virion capture differs by envelope antibody specificity." Journal of virology 88, no. 9 (May 2014): 5165-5170.
Bonsignori, M, Wiehe, K, Grimm, SK, Lynch, R, Yang, G, Kozink, DM, Perrin, F, Cooper, AJ, Hwang, K-K, 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, H-X, Kepler, TB, Montefiori, DC, Mascola, JR, and Haynes, BF. "An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1." The Journal of clinical investigation 124, no. 4 (April 2014): 1835-1843.
Holl, TM, Yang, G, Kuraoka, M, Verkoczy, L, Alam, SM, Moody, MA, Haynes, BF, and Kelsoe, G. "Enhanced antibody responses to an HIV-1 membrane-proximal external region antigen in mice reconstituted with cultured lymphocytes." Journal of immunology (Baltimore, Md. : 1950) 192, no. 7 (April 2014): 3269-3279.
Tomaras, GD, and Haynes, BF. "Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates." Vaccines 2, no. 1 (March 2014): 15-35.