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

Gobeil, Sophie M-C, Rory Henderson, Victoria Stalls, Katarzyna Janowska, Xiao Huang, Aaron May, Micah Speakman, et al. “Structural diversity of the SARS-CoV-2 Omicron spike.” Mol Cell 82, no. 11 (June 2, 2022): 2050-2068.e6. https://doi.org/10.1016/j.molcel.2022.03.028.

PMID
35447081
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Whitley, Jill, Christopher Zwolinski, Christian Denis, Maureen Maughan, Leonie Hayles, David Clarke, Meghan Snare, et al. “Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials.” Transl Res 242 (April 2022): 38–55. https://doi.org/10.1016/j.trsl.2021.11.009.

PMID
34871810
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Li, Dapeng, Simon Brackenridge, Lucy C. Walters, Olivia Swanson, Karl Harlos, Daniel Rozbesky, Derek W. Cain, et al. “Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.” Commun Biol 5, no. 1 (March 28, 2022): 271. https://doi.org/10.1038/s42003-022-03183-5.

PMID
35347236
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Mu, Zekun, Kevin Wiehe, Kevin O. Saunders, Rory Henderson, Derek W. Cain, Robert Parks, Diana Martik, et al. “mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.” Cell Rep 38, no. 11 (March 15, 2022): 110514. https://doi.org/10.1016/j.celrep.2022.110514.

PMID
35294883
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Li, Dapeng, Gregory D. Sempowski, Kevin O. Saunders, Priyamvada Acharya, and Barton F. Haynes. “SARS-CoV-2 Neutralizing Antibodies for COVID-19 Prevention and Treatment.” Annu Rev Med 73 (January 27, 2022): 1–16. https://doi.org/10.1146/annurev-med-042420-113838.

PMID
34428080
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Martinez, David R., Alexandra Schäfer, Sophie Gobeil, Dapeng Li, Gabriela De la Cruz, Robert Parks, Xiaozhi Lu, et al. “A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.” Sci Transl Med 14, no. 629 (January 26, 2022): eabj7125. https://doi.org/10.1126/scitranslmed.abj7125.

PMID
34726473
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Mielke, Dieter, Sherry Stanfield-Oakley, Bhavesh Borate, Leigh H. Fisher, Katelyn Faircloth, Marina Tuyishime, Kelli Greene, et al. “Selection of HIV Envelope Strains for Standardized Assessments of Vaccine-Elicited Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies.” J Virol 96, no. 2 (January 26, 2022): e0164321. https://doi.org/10.1128/JVI.01643-21.

PMID
34730393
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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.” In Npj Vaccines, Vol. 6, 2021. https://doi.org/10.1038/s41541-020-00277-1.

Full Text

Campion, Suzanne L., Elena Brenna, Elaine Thomson, Will Fischer, Kristin Ladell, James E. McLaren, David A. Price, et al. “Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial.” J Clin Invest 131, no. 23 (December 1, 2021). https://doi.org/10.1172/JCI150823.

PMID
34850742
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