Mosquitoes are the vectors of a variety of deadly pathogens. Pathogens have co-evolved with mosquito saliva components to enhance transmission to their mammalian hosts. The saliva proteins and their mechanisms of action are unknown. We are able to inhibit saliva-mediated enhancement of dengue virus and West Nile virus infectivity using a chemical inhibitor. This chemical inhibitor was designed to inhibit serine proteases, suggesting that the saliva protein responsible for enhancement of virus infectivity is a serine protease. Using biochemical separations and analysis of active saliva fractions, we have identified the saliva serine protease that is responsible for the above activity. We hypothesize that a vaccine that targets this saliva protein will limit virus transmission to its host.
Malaria and dengue virus are deadly and destabilizing pathogens. Vaccines that target these pathogens have been difficult to produce due to rapid evolution of the pathogens and complicated immunological issues such as antibody-dependent enhancement. This proposal seeks to develop a novel vaccine that targets vector rather than pathogen components. This strategy avoids the above caveats and will add to the list of tools already in use to prevent exposure to infected arthropods.
Funds raised will be used to purchase C57/B6 mice. These mice will be used as a West Nile virus model of disease. Briefly, we will immunize mice with either whole mosquito saliva, purified saliva serine protease, or mice will be left unimmunized. Mice will be be infected with West Nile alone or with mosquito saliva and we will determine if immunization limits saliva-mediated enhancement of virus infectivity. Extra funds raised will be used to develop a dengue virus mouse model for similar experiments.
This project has the potential to develop a novel type of vaccine that targets vector rather than pathogen components. Additionally, we strive to understand the roles of mosquito saliva serine proteases in the blood feeding process. We hypothesize that these proteins liquify the bite site and facilitate probing and blood feeding. A vaccine that targets these proteins may also limit the ability of a mosquito to feed properly.
I am a Postdoctoral Fellow at Yale University School of Medicine in the Department of Internal Medicine Infectious Diseases. I work in the laboratory of Dr. Erol Fikrig, a world-renowned researcher in vector-borne disease. I have a Ph.D. in Microbiology and Immunology from the Pennsylvania State University College of Medicine. There, I studied interactions between human papillomavirus proteins in human tissues. My passion lies in how viruses evade and utilize the largest immunological barrier to infection - skin.
Anti-serine protease antibodies are currently being made in mice using serine protease peptides. In two weeks, I'll be able to test if these antibodies can deplete and/or inhibit serine protease activity in mosquito saliva. Fingers are crossed.