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

Blasi, Maria, Erich Baker, Elizabeth Brunner, Celia Labranche, David Montefiori, Kevin Saunders, Anthony Moody, et al. “Therapeutic Vaccination With a Combination of IDLV-SIV-Gag and IDLV-PGT121 Results in Prolonged Virus Control in Chronically SHIV-infected Macaques.” In Aids Research and Human Retroviruses, 34:50–50. MARY ANN LIEBERT, INC, 2018.

Scholars@Duke

Verkoczy, Laurent, Chuancang Jiang, Raiees Andrabi, Jinsong Zhang, Amanda Newman, Devin Sok, Ge Song, et al. “Mechanistic Insights Into Vaccine Induction of V2 Apex-directed, Heterologous Tier 2 Neutralizing Responses in CH103 UCA Knock-in Mice.” In Aids Research and Human Retroviruses, 34:110–110. MARY ANN LIEBERT, INC, 2018.

Scholars@Duke

Peachman, Kristina, David Easterhoff, Siriwat Akapirat, Supachai Rerks-Ngarm, Punnee Pittisuttithum, Sorachai Nitayaphan, Sanjay Phogat, et al. “Prolonged Intervals Between Boosts Induces High Magnitude Transient V2-specific Functional Antibodies That Inhibit the Binding of V2 to alpha 4 beta 7 Integrin.” In Aids Research and Human Retroviruses, 34:127–127. MARY ANN LIEBERT, INC, 2018.

Scholars@Duke

Madani, N., A. Princiotto, L. Mach, J. Richard, B. Hora, C. Zhao, T. Bradley, et al. “A CD4-mimetic compound enhances vaccine efficacy against stringent immunodeficiency virus challenge.” In Journal of the International Aids Society, 21:1–1. JOHN WILEY & SONS LTD, 2018.

Scholars@Duke

Madani, Navid, Amy M. Princiotto, Linh Mach, Shilei Ding, Jérémie Prevost, Jonathan Richard, Bhavna Hora, et al. “A CD4-mimetic compound enhances vaccine efficacy against stringent immunodeficiency virus challenge..” Nat Commun 9, no. 1 (June 18, 2018). https://doi.org/10.1038/s41467-018-04758-9.

PMID
29915222
Full Text

Wiehe, Kevin, Todd Bradley, R Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, et al. “Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development..” Cell Host Microbe 23, no. 6 (June 13, 2018): 759-765.e6. https://doi.org/10.1016/j.chom.2018.04.018.

PMID
29861171
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Pardi, Norbert, Michael J. Hogan, Martin S. Naradikian, Kaela Parkhouse, Derek W. Cain, Letitia Jones, M Anthony Moody, et al. “Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses..” J Exp Med 215, no. 6 (June 4, 2018): 1571–88. https://doi.org/10.1084/jem.20171450.

PMID
29739835
Full Text

Song, Hongshuo, Elena E. Giorgi, Vitaly V. Ganusov, Fangping Cai, Gayathri Athreya, Hyejin Yoon, Oana Carja, et al. “Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection..” Nat Commun 9, no. 1 (May 15, 2018). https://doi.org/10.1038/s41467-018-04217-5.

PMID
29765018
Full Text

Kelsoe, Garnett, and Barton F. Haynes. “What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling..” Cold Spring Harb Perspect Biol 10, no. 5 (May 1, 2018). https://doi.org/10.1101/cshperspect.a029397.

PMID
28630077
Full Text

Kisalu, Neville K., Azza H. Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J. Flynn, Brandon K. Sack, Sean Murphy, et al. “A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite..” Nat Med 24, no. 4 (May 2018): 408–16. https://doi.org/10.1038/nm.4512.

PMID
29554083
Full Text

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