Biography
Dr. Bhardwaj was born in Nairobi, Kenya. She came to the United States in 1971 as a college student, graduating from Wellesley College in 1975 with a BA in Biology with honors. Dr. Bhardwaj subsequently spent six years at the New York University where she obtained her M.S., M.D., and PhD degrees. This was followed by a residency in Internal Medicine at the Brigham and Women's Hospital in Boston and a fellowship in Rheumatology at the Hospital for Special Surgery and Weill Medical College in New York. Dr. Bhardwaj continued her research at the Rockefeller University where she was a post-doctoral fellow. She is now an Professor of Medicine in the Department of Pathology and Oncology at New York University School of Medicine. Her focus is on the biology of human dendritic cells and their application in vaccines and immunotherapies for the treatment of chronic virus infections and cancers.
Abstract
Enhancement of anti-HIV Immunity
Although the institution of highly active anti-retroviral therapy (HAART) has reduced morbidity and mortality from HIV-1 infection, the virus persists in tissue reservoirs and rebound viremia occurs when treatment is halted. Recent findings that intermittent compliance with drug therapy stimulates T cell responses have led to the concept that antigenic stimulation through re-exposure to virus, or the boosting of T cell responses via immunization, will be necessary as an adjunct to HAART. We have shown that a highly effective way to generate human anti-viral T cell responses in vivo is by presenting antigens on dendritic cells (DCs) a system of antigen presenting cells (APCs) that stimulate innate and acquired immune responses. This proposal will apply this new modality of enhancing immunity to HIV-1 infection.
The specific aims are to:
- Advance methodology for DC generation from human blood precursors to facilitate DC vaccinations. DCs are currently generated from proliferating or nonproliferating progenitors over 7-14 days. To hasten the generation period and obtain DCs in "good tissue practice" conditions, new procedures and "closed culture" systems will be evaluated.
- Identify effective vaccine vehicles to induce anti-HIV immunity in DC-based immunizations. Current vaccines do not elicit effective cellular immunity against HIV-1, possibly because they fail to target DCs. Innovative vaccines, such as novel DNA constructs, heat shock proteins and chemically inactivated HIV-1, in addition, to nonreplicating pox vectors will be tested for their potential to charge DCs with antigens.
- Establish the safety and immunogenicity of antigen bearing DCs in seronegative and seropositive adults. Clinical trials will be initiated to test the immunogenicity of DCs pulsed with promising vaccines vehicles. We will consider the subset of DC that is the most immunogenic in addition to routes of delivery, schedule and comparison to adjuvants in clinical use.
These studies will provide a basis for designing vaccines which target DCs in situ. In addition, they will support the creation of a vaccine research program at Rockefeller University to train clinical investigators in a new area of immune based therapies.