This project aims to generate new knowledge about enterovirus encephalitis, particularly with EV71 infection which has been the cause of several large epidemics of hand, foot and mouth disease with severe disease involving the central nervous system. In Sarawak we have data collected over 5 years regarding the molecular epidemiology of the virus and we have large collection of virus isolates from mild and severe cases. We have determined that there are several genogroups of EV71 which have been involved in the different outbreaks in the Asia Pacific region in recent times and the challenge is to develop a vaccine against this disease. One of the most important things which need to be done is to understand EV71 encephalitis, and this project will develop an animal model (mouse model) to determine the different parameters of EV71 infection in vivo in order to understand the pathogenesis and the immune response to the virus. These studies will provide the basis for a challenge model for testing vaccines against EV71 disease.

Another objective of the study is to extend the molecular epidemiological studies of EV71 from Sarawak to other parts of Malaysia, particularly the Klang Valley and the East Coast. This will lay the groundwork for field trials of any EV71 vaccine successfully developed by the group.

The final objective of this study is to develop a live virus vectored vaccine against EV71. this vaccine will be based on modified vaccinia Ankara (MVA) which is a smallpox vaccine, and we shall engineer into MVA the major coat protein of EV71 in order to create a recombinant MVA which will deliver the necessary antigens to vaccine recipients. The advantage of using MVA is that we already have experience with the development of an MVA vectored vaccine against dengue.

EXECUTIVE SUMMARY

Project Title:
DEVELOPMENT OF A MOUSE MODEL FOR ENTEROVIRUS ENCEPHALITIS
AND A VACCINE AGAINST EV71

 

In a related project, the team will develop new technologies for the delivery of genes of vaccines and will use EV71 as a model for these new technologies. The mouse model developed in this project will also be used to evaluate the new technologies.

Period of the project : 3 Years (2001 - 2004)

Achievements

Progress/Achievements for year one

New Process : Refer to Appendix 2

Discovery :

1- Recombinant VP1 from 3 different genotypes of ev71 have been cloned, expressed and tested for antigenicity. All are well expressed and recognised by monoclonal antibodies against EV 71.
2- Purified recombinant VP1 has been used to immunize mice and rabbits and antisera of very high titre has been generated. The results of this work is attached in appendix