Vaccine strain selection for FMD serotype O and A viruses in South East Asia and

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

Foot and mouth disease (FMD), caused by FMD virus (FMDV) is a highly contagious and economically devastating viral disease affecting cloven hoofed animals including cattle, sheep, goats and pigs. The disease is endemic in Asia including South East Asia (SEA), Africa, Middle East and some part of South America whereas Australia, North America and Europe are free from FMD. FMDV is a RNA virus, and due to lack of proof reading activity of the viral RNA polymerase and quasi-species nature of the virus, new antigenic variants can evolve rapidly resulting in existence of 7 serotypes and many subtypes within a serotype. Vaccination against one serotype does not provide cross protection against other serotypes and sometimes one subtype to other subtype within a serotype. Currently FMD is highly endemic in SEA and East Asia (EA) countries with three circulating serotypes (serotype O is the most predominant serotype followed by Serotype A and Asia1) causing a threat to Australia and other free countries. Although vaccination is one of the most important control measures to prevent FMD outbreaks, the available vaccines may not be able to provide enough cross protection against the circulating FMDV in these countries due to emergence of new lineages and sub lineages within a serotype. This has been experienced in South Korea during 2010, a FMD free country, when a new lineage of serotype O FMDV spread in to the country and the existing O1Manisa vaccine could not provide full protection. So a regular vaccine matching test of circulating viruses with the existing vaccines is required and if necessary a broad cross reacting vaccine strain should be selected, adapted and incorporated to the existing vaccine reserves. Therefore the main aim of this project is to match circulating virus strains with existing vaccines and new putative vaccine strains to find out a suitable vaccine that provide maximum cross protection against the newly emerging viruses circulating in this region. The current methods of vaccine matching and strain selection mainly rely on serological tests that use polyclonal anti-sera raised against vaccines and comparing the reactivity of these antisera with the vaccine strains and the field isolates. However, these serological tests are time consuming and not fully reliable due to day to day variation of the tests, cell types, and operators, so there is a great need for the development of an alternative approach to this serological test. Since the antigenic determinants of FMDV are associated with the viral capsid, capsid sequences of vaccine strains and circulating viruses may provide an alternative dataset for selection of an appropriate cross reacting vaccine. By using serological and capsid sequence data, amino acid residues specially involved in cross protection which would have a direct impact on the antigenicity of the virus, can be identified. Then the effect of a change in these amino acid residues on the antigenic nature of the virus can be studied by mutating the residues in an existing cDNA clone using reverse genetics technique. This can help to design a new vaccine, which can give better cross protection against the circulating viruses.
This project addresses the wider need to develop simplified vaccine selection techniques that would be mainly beneficial for the scientific community. In order to BBSRC priorities, this project will align with 'Agriculture and Food Security'.


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Project Reference Relationship Related To Start End Student Name
BB/M011224/1 01/10/2015 31/03/2024
1801898 Studentship BB/M011224/1 01/10/2016 30/09/2020