Infectious Animal Model of Enterovirus and Applications in Vaccine Development (I)

Enterovirus 71 (EV71) and coxsackievirus B3 (CVB3) are the most common causative factors for hand, foot, and mouth disease (HFMD) and neurological disorders in children. EV71 has emerged as the neuroinvasive virus responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Based on phylogenetic analysis of the most variable VP1 gene, EV71 has been classified into three major genogroups (A, B, and C) including 11 genotypes (A, B1-B5, and C1-C5). The vaccine strain developed by Medigen Vaccine Biologics is B4, which differs from the current predominant genotype B5 circulating in Taiwan and Southeast Asia. This project has the following aims specific aims: (1) Conducting a phylogenetic analysis of the EV71 strains isolated at Chang Gung Memorial Hospital between 2000-2013. Based on these results, we will show that which EV71 genotypes circulated endemically in Taiwan during this period. (2) Establishing different genotype mouse-adapted EV71 and CVB3. We will generate after four serial passages of the parental EV71 and CVB3 strains in mice. We will use the different mouse-adapted different EV71 genotype to evaluate the cross-reactive neutralizing antibody titers of the vaccine. Furthermore, the mouse-adapted CVB3 will be used to infect mice for antivirus drug study in the future. (3) Evaluating the protective efficacy of the Medigen vaccine by using neonatal mice and human SCARB2 (hSCARB2) transgenic mice. The absence of a reliable animal model is a problem in evaluating the cross-reactive neutralizing antibody titers of a vaccine. We will develop a new EV71 animal model by using a different genotype virus strain to infect neonatal mice and hSCARB2-transgenic mice that expressing the discovered EV71 hSCARB2 receptor. Appropriate animal models are required to understand enterovirus neuropathogenesis more clearly and to facilitate the developing of effective vaccines and drugs. The results of this proposed study could provide a new reliable animal model for studying antiviral drugs and vaccines for enteroviruses.

Project ID:PC10410-0039
External Project ID:MOST104-2622-B182-002-CC2