Humoral Immunology Section
Richard Koup, M.D.
Major Areas of Research
- Characterize protective immune responses against HIV-1 with a focus on B cells
- Study the natural immune response to HIV-1
- Develop novel strategies for vaccine design
The Humoral Immunology Section (HIMS) focuses on understanding antibody-mediated protective immune responses against HIV-1 using studies of both the plasma antibody compartment and the B-cell compartment. The goal of these studies is to elucidate mechanisms of virus neutralization and the viral epitopes targeted by neutralizing antibodies and to translate this information into novel strategies for vaccine design. Our laboratory works closely with the structural biology laboratories at the VRC to design and evaluate novel vaccines. New vaccine immunogens are designed based on the latest information from the atomic level structure of the HIV-1 Env glycoprotein complexed to neutralizing antibodies. Our laboratory evaluates the antibody specificities elicited by these vaccines, including the neutralizing activity of sera and the viral epitopes that are vulnerable to neutralizing antibodies. Molecular reporter virus assays allow the study of diverse virus isolate from various regions of the world to understand the effect of genetic and antigenic diversity and viral escape on neutralizing antibody responses.
We also study the natural immune response to HIV-1 by analyzing the development of serum antibody responses and by analyzing B-cell responses at the level of single antigen-specific B-cells. Such methodologies allow a detailed dissection of the humoral immune response to HIV-1 with the goal of understanding how a broadly reactive neutralizing antibody response develops during the course of natural HIV-1 infection and understanding how the humoral immune system targets vulnerable regions on the HIV-1 Env glycoprotein. Multicolor flow cytometry is used to study the B-cell compartment and to identify antigen-specific B-cells from which monoclonal antibodies can be isolated. The PCR-based reconstitution of HIV-1 specific monoclonal antibodies from B cells, together with deep sequencing of antibody gene transcripts, allows us to track the evolution of the humoral immune response against HIV-1 and to interrogate mechanisms of viral immune evasion from neutralizing antibodies. The information from these pathogenesis studies, together with studies of the antibody response elicited by vaccine immunogens, is used to inform the design of improved antibody-based vaccines for HIV-1.
For more information on research conducted by the Humoral Immunology Section, visit the Humoral Immunology Core.
M.D., 1982, Johns Hopkins University School of Medicine, Baltimore, MD
M.S., 1979, University of Connecticut, Stamford, CT
B.S., 1978, University of Connecticut, Stamford, CT
Dr. Koup received his B.S. in biophysics in 1978 and his M.S. in biochemistry in 1979 from the University of Connecticut. He attended Johns Hopkins University School of Medicine, where he obtained his M.D. in 1982. Dr. Koup served an internship and residency in internal medicine with the Rhode Island Hospital, Brown University Medical School, Providence, Rhode Island, from 1982 to 1985. He served in a clinical fellowship (infectious diseases) at the Worcester Memorial Hospital and a research fellowship (viral immunology), at UMass Medical Center, Worcester. Dr. Koup is board certified in both internal medicine and infectious diseases. Dr. Koup previously held several academic appointments at the University of Texas Southwestern Medical Center that include chief, division of infectious disease; professor, internal medicine; professor, microbiology; and the Jay P. Sanford Professor of Infectious Diseases.
The Humoral Immunology Section studies the antibody response to HIV-1 and SARS-COV-2 infection or vaccination. Ongoing research focuses on antibody discovery and antibody-virus co-evolution in infected patients or non-human primate models, with the goals of providing templates for vaccine design and antibodies with potential for clinical utility in preventing or treating infection.