Identifying epitopes that induce antibody mediated protection against foot-and-mouth disease using reverse genetics

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FMDV causes a highly contagious and economically devastating disease of domestic animals and is generally controlled by vaccination in endemic countries and restriction of animal movement and slaughter of infected and in-contact animals in FMD-free countries. The recent 2001 outbreaks in the United Kingdom have significantly increased public awareness of this disease and now there is heightened interest in a "vaccinate to-live-policy". Current FMD vaccines are serotype specific and may fail to protect fully against subtypes. Vaccines therefore have to be selected, currently based on serological match between vaccine strain and field isolate. The mechanism for FMD vaccine induced protection is not clear with respect to both the viral determinants of protection and the role of different immune responses. Antibody mediated protection is believed to be an important component as there is a strong correlation between antibody titre and protection. Various neutralising epitopes have been identified on the surface of the FMD virus using murine MAb escape mutants. In addition there is evidence for the existence of other non-neutralising epitopes that are believed to play a significant role. The relative importance of different epitopes has not been ascertained. This project will help to define viral determinants of antibody mediated protection which will help in the development of sequence-based vaccine selection methods and novel broadly cross-reactive vaccines. Using reverse genetics approach a recombinant virus will be generated that is identical to its parent except that the major antigenic sites will be mutated until no serological cross-reaction between the mutant and its parent. Once it has been shown that the mutant virus does not elicit antibodies able to protect against a parental virus infection, the contribution of the different epitopes to serological recognition and in vivo protection will be established by reconstituting each epitope one at a time.

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