Project Description

Rebecca Visser
Animal, Dairy, and Veterinary Sciences
Mentor: Dr. Young- Min Lee
Construction of a Live Chimeric Zika Vaccine Through the Expression of Viral Envelope Proteins

Zika virus (ZIKV), a mosquito-borne flavivirus, has become a global health concern due to an unprecedented large outbreak in the Americas. ZIKV is phylogenetically related to other flaviviruses, such as Japanese encephalitis (JEV), West Nile, dengue, and yellow fever viruses. Although ZIKV infection generally causes no symptoms or a mild self-limiting illness, it has recently been linked with congenital neurological malformations (microcephaly) in infants and neuroimmunological complications (Guillain-Barré syndrome) in adults. Despite its emergence as an important public health problem, little is known about ZIKV biology, and neither vaccine nor drug is available to control ZIKV infection. The focus of this study is to develop a new chimeric vaccine candidate against ZIKV, by utilizing a clinically proven live-attenuated JEV vaccine, SA14-14-2, as a vector and replacing the neutralizing antibody-inducing envelope (E) gene of JEV with the corresponding gene of ZIKV. To this end, we used our infectious cDNA clones of JEV and ZIKV to create the chimeric JEV/ZIKV virus as a vaccine candidate. Recently, we recovered the chimeric viruses from BHK-21 cells transfected with infectious RNAs transcribed in vitro from the cloned cDNA. Now, we are in the process of determining safety, immunogenicity, and protective efficacy of our vaccine candidate in type 1 interferon knock-out (IFNAR) mice. Our results will provide a new JEV-based platform for the development of chimeric vaccines against ZIKV and other pathogenic flaviviruses.