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
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

Eslamizar, L., C. Petrovas, D. J. Leggat, K. Furr, M. L. Lifton, G. Levine, S. Ma, et al. “Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center (Accepted).” In Npj Vaccines, Vol. 6, 2021. https://doi.org/10.1038/s41541-020-00277-1.

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Li, Dapeng, Robert J. Edwards, Kartik Manne, David R. Martinez, Alexandra Schäfer, S Munir Alam, Kevin Wiehe, et al. “In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.” Cell, June 18, 2021. https://doi.org/10.1016/j.cell.2021.06.021.

PMID
34242577
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Shiakolas, Andrea R., Kevin J. Kramer, Daniel Wrapp, Simone I. Richardson, Alexandra Schäfer, Steven Wall, Nianshuang Wang, et al. “Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions.” Cell Rep Med 2, no. 6 (June 15, 2021): 100313. https://doi.org/10.1016/j.xcrm.2021.100313.

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34056628
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Saunders, Kevin O., Esther Lee, Robert Parks, David R. Martinez, Dapeng Li, Haiyan Chen, Robert J. Edwards, et al. “Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.” Nature 594, no. 7864 (June 2021): 553–59. https://doi.org/10.1038/s41586-021-03594-0.

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33971664
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Cai, Fangping, Wei-Hung Chen, Weimin Wu, Julia A. Jones, Misook Choe, Neelakshi Gohain, Xiaoying Shen, et al. “Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.” Plos Pathog 17, no. 6 (June 2021): e1009624. https://doi.org/10.1371/journal.ppat.1009624.

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34086838
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Williams, Wilton B., R Ryan Meyerhoff, R. J. Edwards, Hui Li, Kartik Manne, Nathan I. Nicely, Rory Henderson, et al. “Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.” Cell 184, no. 11 (May 27, 2021): 2955-2972.e25. https://doi.org/10.1016/j.cell.2021.04.042.

PMID
34019795
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Parker, Robert, Thomas Partridge, Catherine Wormald, Rebeca Kawahara, Victoria Stalls, Maria Aggelakopoulou, Jimmy Parker, et al. “Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells.” Cell Rep 35, no. 8 (May 25, 2021): 109179. https://doi.org/10.1016/j.celrep.2021.109179.

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34004174
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Shen, Xiaoying, Haili Tang, Charlene McDanal, Kshitij Wagh, William Fischer, James Theiler, Hyejin Yoon, et al. “SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines.” Cell Host Microbe 29, no. 4 (April 14, 2021): 529-539.e3. https://doi.org/10.1016/j.chom.2021.03.002.

PMID
33705729
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Saunders, Kevin O., Norbert Pardi, Robert Parks, Sampa Santra, Zekun Mu, Laura Sutherland, Richard Scearce, et al. “Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates.” Npj Vaccines 6, no. 1 (April 9, 2021): 50. https://doi.org/10.1038/s41541-021-00307-6.

PMID
33837212
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Tolbert, William D., Verna Van, Rebekah Sherburn, Marina Tuyishime, Fang Yan, Dung N. Nguyen, Sherry Stanfield-Oakley, et al. “Erratum for Tolbert et al., "Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial".” Mbio 12, no. 2 (April 6, 2021). https://doi.org/10.1128/mBio.00474-21.

PMID
33824213
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