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.