Barton Ford Haynes, MD

Professor of Medicine
Frederic M. Hanes Distinguished 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

D’Souza, M Patricia, Shyam Rele, Barton F. Haynes, Dale J. Hu, David L. Kaplan, Shadi Mamaghani, and David Rampulla. “Engineering immunity for next generation HIV vaccines: The intersection of bioengineering and immunology..” Vaccine 38, no. 2 (January 10, 2020): 187–93. https://doi.org/10.1016/j.vaccine.2019.10.036.

PMID
31759734
Full Text

Finney, Joel, Guang Yang, Masayuki Kuraoka, Shengli Song, Takuya Nojima, Laurent Verkoczy, Daisuke Kitamura, Barton F. Haynes, and Garnett Kelsoe. “Cross-Reactivity to Kynureninase Tolerizes B Cells That Express the HIV-1 Broadly Neutralizing Antibody 2F5..” J Immunol 203, no. 12 (December 15, 2019): 3268–81. https://doi.org/10.4049/jimmunol.1900069.

PMID
31732530
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Saunders, Kevin O., Kevin Wiehe, Ming Tian, Priyamvada Acharya, Todd Bradley, S Munir Alam, Eden P. Go, et al. “Targeted selection of HIV-specific antibody mutations by engineering B cell maturation..” Science 366, no. 6470 (December 6, 2019). https://doi.org/10.1126/science.aay7199.

PMID
31806786
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Paes, Wayne, German Leonov, Thomas Partridge, Takayuki Chikata, Hayato Murakoshi, Anna Frangou, Simon Brackenridge, et al. “Contribution of proteasome-catalyzed peptide cis-splicing to viral targeting by CD8+ T cells in HIV-1 infection..” Proc Natl Acad Sci U S A 116, no. 49 (December 3, 2019): 24748–59. https://doi.org/10.1073/pnas.1911622116.

PMID
31748275
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LaBranche, Celia C., Rory Henderson, Allen Hsu, Shay Behrens, Xuejun Chen, Tongqing Zhou, Kevin Wiehe, et al. “Correction: Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies..” Plos Pathog 15, no. 12 (December 2019). https://doi.org/10.1371/journal.ppat.1008200.

PMID
31790514
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Easterhoff, David, Justin Pollara, Kan Luo, William D. Tolbert, Brianna Young, Dieter Mielke, Shalini Jha, et al. “Boosting with AIDSVAX B/E enhances Env constant region 1 and 2 antibody-dependent cellular cytotoxicity breadth and potency..” J Virol, November 27, 2019. https://doi.org/10.1128/JVI.01120-19.

PMID
31776278
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Wee, Edmund G., Nathifa A. Moyo, Kevin O. Saunders, Celia LaBranche, Filippo Donati, Silvia Capucci, Robert Parks, et al. “Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1..” Mol Ther Methods Clin Dev 14 (September 13, 2019): 148–60. https://doi.org/10.1016/j.omtm.2019.06.003.

PMID
31367651
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LaBranche, Celia C., Rory Henderson, Allen Hsu, Shay Behrens, Xuejun Chen, Tongqing Zhou, Kevin Wiehe, et al. “Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies..” Plos Pathog 15, no. 9 (September 2019). https://doi.org/10.1371/journal.ppat.1008026.

PMID
31527908
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Bricault, Christine A., Karina Yusim, Michael S. Seaman, Hyejin Yoon, James Theiler, Elena E. Giorgi, Kshitij Wagh, et al. “HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design..” Cell Host Microbe 26, no. 2 (August 14, 2019). https://doi.org/10.1016/j.chom.2019.07.016.

PMID
31415756
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