Center for Clinical and Translational Science

Dr. Marina Caskey, former Clinical Scholar and one of the inaugural class of 2009 graduates of the Master’s degree in Clinical and Translational Science, was awarded five years support on a Mentored Patient-Oriented Research Career Development Award (K23) from the National Institutes of Health. The purpose of the K23 award is to support the career development of investigators who have made a commitment to focus their research endeavors on patient-oriented research.

Dr. Caskey’s project, titled Characterization of the Immunity Induced by a DEC205-targeted HIV Vaccine, received funding in September 2009. This award will support Dr. Caskey’s HIV vaccine research while she is still under the expert mentorship of Dr. Ralph Steinman, Dr. Sarah Schlesinger, and Dr. Martin Markowitz. The goal of Dr. Caskey’s project is to evaluate the immune responses induced by a novel HIV vaccine. There are unprecedented challenges to the development of an effective HIV vaccine, such as the extraordinary viral diversity of HIV-1 and the lack of clear immune correlates of protection. To date, two vaccine strategies tested in efficacy trials have failed to induce protection. The vaccine strategy developed in Dr. Steinman’s laboratory focuses on directly exploiting dendritic cells’ potential to improve the magnitude and quality of immune responses, either alone or in combination with other strategies. HIV antigens are delivered within fusion monoclonal antibodies (mAB) directly to maturing dendritic cells via DEC-205, an endocytic dendritic cell receptor. Previous research has shown that prime-boost immunization with anti-DEC-205 HIV Gag p24 fusion mAb with poly IC as an adjuvant induces protective immunity in mice. In addition, there are preliminary data showing that targeting of HIV antigens via DEC-205 receptor, in Peripheral Blood Mononuclear Cells from HIV-infected individuals, induces both HIV-specific CD4+ and CD8+ T cell recall responses. The studies Dr. Caskey has proposed will investigate the primary immune responses generated by DEC-targeted HIV vaccines in healthy volunteers. The proposed immunological assays may prove useful for the evaluation of future HIV vaccine candidates. These studies will also investigate optimal choices of HIV immunogens to achieve broader viral coverage without compromise of antigen processing and presentation. If successful, this vaccine approach will add to the current arsenal of HIV vaccine strategies.

Dr. Caskey stated, “At the end of the five-year award period, I will have a greater understanding of basic immunology and the immune responses induced after vaccination. I will also have gained experience from the design and execution of an early phase clinical trial of a novel compound. I believe that I will be able to use this knowledge in immunology and immunological methods in the evaluation and development of future HIV vaccine candidates.” Dr. Caskey went on to explain how the Clinical Scholars Program prepared her for the research project proposed in her K-award, “The program taught me invaluable insights into translational research, biostatistics, and the conduct of ethical research. Since graduating from the Clinical Scholars Program, I have continued to acquire the skills necessary for a successful independent research career.”