Prof David Paton

There is a strong desire to develop vaccination policies for FMD that would reduce reliance on large scale slaughtering of animals. However, vaccinated animals may sometimes become infected without showing signs of disease and pose a risk of starting new outbreaks later on if the virus persists in these animals. Therefore, more effective vaccines are needed to better block virus establishment and that do not induce antibodies against some of the immunogenic viral proteins produced during a wild-type infection. To strengthen the immune response to vaccination, we are investigating vectored FMD vaccines to elicit better cell mediated and mucosal immunity. On diagnostics, we are developing and validating tests that differentiate infection from vaccination including a test for FMD-specific IgA in saliva and alternative format tests for FMD virus non-structural antibody detection. The development and validation of marker vaccines and associated diagnostics will enable animals to be effectively vaccinated without precluding the possibility to detect any vaccinated animals that have become infected and pose a risk for disease spread.

Vaccine selection is also of great importance in FMD control because of the existence of seven different virus serotypes and multiple antigenic subtypes. Current methods rely on serological tests to match vaccine strains to field isolates, but these are slow and depend upon serological reagents that are hard to standardise. Furthermore, there is a paucity of validation of serological matching approaches due to the costs of in vivo cross-protection tests. An alternative approach would be to relate antigenic phenotype to the derived amino acid sequence of viral capsids. Therefore, another focus of our work is the study of epitope conservation and significance in protection, investigated by means of sequence analyses and reverse genetics. Better definition of protective epitopes and their relative conservation may also help to create more broadly protective vaccines.

Finally, we are interested in ways to predict vaccine induced protection. At one level this work is attempting to identify immune correlates and at the population level we are collating data on the ability of vaccination to block viral transmission in order to design optimal vaccination strategies and predict vaccine efficacy in emergency situations.