I began working in Dr. David Weiner's laboratory at the University of Pennsylvania to pursue my interests in the basic science of host- pathogen interactions and the application of newly acquired knowledge to develop candidate vaccines. I am pursuing the Mentored clinical Scientist Development Award (K08) to further my research and analytic skills in the areas of primate immunology and vaccinology. The K08 award allows for the acquisition and refinement of these skills through a program of coursework in immunology and virology and the progressive research program outlined below. The spread of HIV-1 has resulted in significant morbidity and mortality worldwide. While the use of multi-drug anti-retroviral regimens appears promising, the most cost effective means to control the HIV epidemic lies in the application of mass immunization strategies. Vaccines based on nucleic acids provide a promising new potential strategy for the prevention or control of HIV-1 infection and its progression to Acquired immunodeficiency syndrome (AIDS). Dr. Wiener's laboratory has accumulated extensive experience in the development of genetic vaccines, especially in the area of HIV-1 infection. Recently, we reported the protection of adult chimpanzees from HIV-1 challenge by genetic vaccination. In addition, adult chimpanzees already infected with HIV-1 have exhibited a sustained decrease in viral load to unmeasurable levels after immunization with the same genetic vaccines. As a pediatrician whose clinical and research interests have centered around the HIV epidemic I can think of no better project than one which investigates the effects of a promising new vaccine technology of immature subjects. Immature hosts respond to traditional vaccines with qualitative and quantitative differences when compared to adults. For instance, human immunoglobulin production only reaches adult levels at age two years and responses to certain live attenuated vaccines (measles, etc.) have been disappointing in younger infants. In an effort to build on Dr. Weiner's findings in adult animals and extend them to the most likely target population for mass immunization strategies (i.e. infants and children) I have begun preliminary investigations into the immunogenecity and safety of genetic immunization in immature primates. I intend to comprehensively characterize the immunogenecity and safety of genetic vaccination against HIV-1 in infant chimpanzees with the ultimate aim of demonstrating protection from viral challenge. I will also investigate the concomitant use of molecular adjuvant genes such as IL-10, IL-12, GMCSF and B7 costimulatory molecules in preliminary murine and parallel primate experiments in an effort to engineer specific immune responses. I further propose to find whether the correlates of protection will be similar to those seen in adults. The overall goal of this proposal is to characterize the potential of genetic immunization of induce relevant and therefore protective immune responses against HIV-1 immunologically immature chimpanzees and ultimately in humans. These studies will have added importance to the general application of genetic immunization against any disease of children.
| Bagarazzi, M L; Boyer, J D; Javadian, M A et al. (1999) Systemic and mucosal immunity is elicited after both intramuscular and intravaginal delivery of human immunodeficiency virus type 1 DNA plasmid vaccines to pregnant chimpanzees. J Infect Dis 180:1351-5 |
