School of Biodiversity, One Health & Veterinary Medicine

Dr Richard Reeve & Prof. Dan Haydon (IBAHCM), with Don King (Pribright)

An effective vaccination programme for the eradication of foot-and-mouth disease from India

Foot-and-mouth disease (FMD) is a global social and economic burden. Worldwide, ~3 billion doses of vaccine are used. The Indian Government plans to use ~800 million doses of trivalent vaccine annually and the UK has a policy encompassing emergency vaccination in case of FMD outbreaks. However, vaccination is constrained by lack of or incomplete inter and intra serotype cross-protection and by cost and vaccine production capacity.

Our scientific aims address (1) the problems of narrow-spectrum antigenic protection elicited by FMD vaccines and (2) the need to monitor the effectiveness of vaccination programmes and to target vaccine use.

Our objectives are to develop new approaches to (a) improve predictions of the need for and value of new vaccine strains; (b) produce more broadly cross-reactive vaccines; (c) monitor viral circulation in vaccinated areas, and (d) evaluate vaccine performance in the field and target vaccine use.

This will be delivered by bringing together FMD research and control expertise in India and the UK. The Project Directorate on FMD (PDFMD) is responsible for surveillance, diagnosis and epidemiology of FMD in India and Indian Immunologicals (IIL) is the largest Indian FMD vaccine producer. The Pirbright Institute (PIR) is a leading centre for FMD research and diagnosis and collaborates extensively with the University of Glasgow (UoG) to benefit from expertise in quantitative epidemiology and antigenic modelling, and with the Istituto Zooprofilattico Sperimentale in Brescia (IZSLER) who have renowned monoclonal antibody (mAb) collections.

1. Overcoming the problems of narrow-spectrum antigenic protection elicited by FMD vaccines. The antigenic determinants of FMDV that elicit protective antibodies are on the virus surface. We hypothesise that as with other antigenically variable viruses, the dominant epitopes here act as decoys, subverting the immune response from recognition of conserved features. We will generate a model to understand the dominance of antigenic sites, and infer antigenic relationships between viruses for vaccine strain selection. Secondly, we will use cross-reactive mAbs to help identify conserved epitopes for incorporation into new, more broadly protective vaccines. PDFMD will undertake serological and sequencing studies of their extensive virus collections with help from UoG for data modelling. IZSLER will provide existing mAbs augmented by new ones prepared and selected with automated hybridoma screening technology at IIL. PIR will provide reverse genetics to test epitope findings and will quantify antibody-virus cross-protection.

2. Monitoring the effectiveness of the vaccination programme and evaluating targeted vaccine use. We will develop systems to accurately measure virus circulation in the field and identify the impact that vaccination is having on this. Systems for detecting antibodies and for detecting and characterising viral RNA in milk using type/strain-specific assays will be established along with methodologies to infer the extent of continuing virus circulation from the genetic diversity that is revealed from sequencing these viruses. Longitudinal field studies and sample collections will be targeted to areas at different stages of FMD control. These unbiased approaches will be combined with existing and new field data to inform future models to identify the spatial and temporal distribution of specific serotypes of FMDV in the country. This work will be carried out by PDFMD with technical support from PIR and UoG.

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First published: 13 January 2016