EVALUATION OF TRANSMISSION POTENTIAL OF TWO CHIMERIC CHIKUNGUNYA VACCINE CANDIDATES IN AEDES MOSQUITOES

Justin Darwin, S.C. Weaver, Ph.D.¹, J. Kenney, E. Wang, Ph.D.¹, E. Volkova², and E. Frolova, Ph.D.²

¹Department of Pathology; ²Department of Microbiology and Immunology UTMB

Introduction: The development of infectious cDNAs for alphaviruses opened the opportunity to explore their attenuation by extensively modifying the viral genomes, an approach that might minimize or exclude the reversion to the wild-type, pathogenic phenotype. Chikungunya virus (CHIKV) is an emerging alphavirus that has caused major epidemics in India and Africa since 2005. Objective: Because there is no licensed human vaccine, and an attenuated Investigational New Drug product developed by the U.S. Army causes mild arthritis in some vaccinees, we developed chimeric alphavirus vaccine candidates using the non-structural genes of either Venezuelan equine encephalitis attenuated vaccine strain TC-83, or a naturally attenuated strain of eastern equine encephalitis virus (EEEV) and the structural genes of CHIKV. Both vaccine candidates replicated efficiently in cell cultures and were highly attenuated in mice. In addition, vaccinated mice were protected from viremia and disease after challenge with wild type CHIKV. Because the transmission of live alphavirus vaccine strains is undesirable due to the potentially unpredictable evolution of these viruses during natural transmission cycles as well as the potential for reversion, we evaluated the transmission potential for these vaccine candidates in Ae. Aegypti and Ae. Albopictus mosquitoes. Methods: We assessed the transmission potential by exposing Aedes mosquitoes to artificial blood meals containing high titers of virus and then assaying for overall infection and dissemination. Results: Both vaccine candidates exhibited a decreased rate of infection and dissemination compared to the parent alphaviruses. Conclusion: the greatly attenuated phenotype of this genetically engineered virus and its diminished ability to replicate in mosquito cells suggest a new approach for generating live alphavirus vaccine strains. Supported by NIAID through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, NIH grant # U54 AI057156.