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

Pardi, Norbert, Celia C. LaBranche, Guido Ferrari, Derek W. Cain, István Tombácz, Robert J. Parks, Hiromi Muramatsu, et al. “Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques..” Molecular Therapy. Nucleic Acids 15 (April 2019): 36–47. https://doi.org/10.1016/j.omtn.2019.03.003.

PMID
30974332
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LaBranche, Celia C., Andrew T. McGuire, Matthew D. Gray, Shay Behrens, Xuejun Chen, Tongqing Zhou, Quentin J. Sattentau, et al. “Correction: HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies..” Plos Pathogens 15, no. 3 (March 26, 2019). https://doi.org/10.1371/journal.ppat.1007646.

PMID
30913265
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Krebs, Shelly J., Young D. Kwon, Chaim A. Schramm, William H. Law, Gina Donofrio, Kenneth H. Zhou, Syna Gift, et al. “Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual..” Immunity 50, no. 3 (March 12, 2019): 677-691.e13. https://doi.org/10.1016/j.immuni.2019.02.008.

PMID
30876875
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Petitdemange, Caroline, Sudhir Pai Kasturi, Pamela A. Kozlowski, Rafiq Nabi, Clare F. Quarnstrom, Pradeep Babu Jagadeesh Reddy, Cynthia A. Derdeyn, et al. “Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques..” Jci Insight 4, no. 4 (February 21, 2019). https://doi.org/10.1172/jci.insight.126047.

PMID
30830870
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Bresk, C Anika, Tamara Hofer, Sarah Wilmschen, Marina Krismer, Anja Beierfuß, Grégory Effantin, Winfried Weissenhorn, et al. “Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector..” Viruses 11, no. 2 (February 15, 2019). https://doi.org/10.3390/v11020159.

PMID
30769947
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Henderson, Rory, Brian E. Watts, Hieu N. Ergin, Kara Anasti, Robert Parks, Shi-Mao Xia, Ashley Trama, et al. “Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodies..” Nature Communications 10, no. 1 (February 8, 2019). https://doi.org/10.1038/s41467-019-08415-7.

PMID
30737386
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Kisalu, Neville K., Azza H. Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J. Flynn, Brandon K. Sack, Sean Murphy, et al. “Author Correction: A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite..” Nature Medicine 25, no. 1 (January 2019): 188–89. https://doi.org/10.1038/s41591-018-0315-0.

PMID
30552419
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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 25, no. 1 (January 2019): 59-72.e8. https://doi.org/10.1016/j.chom.2018.12.001.

PMID
30629920
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Bonsignori, Mattia, Eric Scott, Kevin Wiehe, David Easterhoff, S Munir Alam, Kwan-Ki Hwang, Melissa Cooper, et al. “Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier..” Immunity 49, no. 6 (December 11, 2018): 1162-1174.e8. https://doi.org/10.1016/j.immuni.2018.10.015.

PMID
30552024
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Eeden, Charmaine van, Constantinos Kurt Wibmer, Cathrine Scheepers, Simone I. Richardson, Molati Nonyane, Bronwen Lambson, Nonhlanhla N. Mkhize, et al. “V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity..” Cell Reports 25, no. 11 (December 2018): 3123-3135.e6. https://doi.org/10.1016/j.celrep.2018.11.058.

PMID
30540944
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