Title: Improving CSFV control through enhanced diagnostic and intervention tools
Funder: Department for Environment, Food and Rural Affairs

Abstract: Description An outbreak of classical swine fever (CSF), a highly infectious disease, would have substantial negative impacts on the UK swine industry. Effective live- attenuated vaccines that rapidly protect against CSF exist. However, it is not possible to distinguish the presence of wild-type infectious classical swine fever virus (CSFV) in herds that are vaccinated with these vaccines. The use of these vaccines is limited in the UK as the subsequent inability to identify wild-type virus by serological tests would impede international trade in pigs and pig products. Control of any future outbreak of CSF is, therefore, still reliant on rapid detection of disease, movement restrictions, elimination of infected herds and, potentially, pre-emptive culling. This project aims to enhance the control of CSFV by improving diagnostic tools and developing interventions that rapidly detect disease and prevent it from spreading. To achieve this we will establish the serological fingerprints induced in pigs infected with wild-type CSFV, vaccine strains and with related ruminant pestiviruses, which also infect pigs and complicate CSFV diagnosis, and identify differences that can be exploited for new differential diagnostic tools. We will exploit developments in genome sequencing technologies to enhance methods to allow rapid molecular characterisation to assist tracing of virus movements in real-time during an outbreak. To facilitate rapid disease control we will investigate the use of virally-vectored antiviral immune molecules as a metaphylactic intervention that could be applied in zones surrounding an outbreak to prevent disease from spreading.A critical objective of the project is to enhance understanding of the mechanisms by which the existing live-attenuate vaccines, which aren’t used due to the lack of discrimination of infection and vaccination, induce rapid and effective protection to facilitate the rational design of vaccines that do discriminate. Specifically, we aim to characterise the interactions of vaccine virus and virulent virus with immune cells, in particular dendritic cells located the primary site of virus replication in the tonsils, to identify the triggers that lead to an effective protection as opposed to interactions that lead to disease. To generate a rapidly-acting, efficacious and discriminatory vaccine for the field we will investigate the ability of intranasal delivery of nanoparticle-based vaccine candidates to stimulate effective immune responses. Finally, viral vectors encoding multiple factors required for protection against CSFV will be generated as potential vaccine candidates Objective Objective 1: Enhancing the control of CSFV through improved diagnostic tools and metaphylactic intervention.Objective 2 Understanding the mechanisms of CSFV c-strain vaccines for the rational design of DIVA vaccinesObjective 3 Improving prophylactic and emergency vaccination against CSFV


Research activity codes: 3.4 VACCINES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION