Review : Capripoxvirus Diseases: Current Status and Opportunities for Control

Lumpy skin disease, sheeppox and goatpox are high-impact diseases of domestic ruminants with a devastating effect on cattle, sheep and goat farming industries in endemic regions. In this article, we review the current geographical distribution, economic impact of an outbreak, epidemiology, transmission and immunity of capripoxvirus. The special focus of the article is to scrutinize the use of currently available vaccines to investigate the resource needs and challenges that will have to be overcome to improve disease control and eradication, and progress on the development of safer and more effective vaccines. In addition, field evaluation of the efficacy of the vaccines and the genomic database available for poxviruses are discussed.Peer reviewe

Foot-and-Mouth Disease Virus Persists in the Light Zone of Germinal Centres

Foot-and-mouth disease virus (FMDV) is one of the most contagious viruses of animals and is recognised as the most important constraint to international trade in animals and animal products. Two fundamental problems remain to be understood before more effective control measures can be put in place. These problems are the FMDV “carrier state” and the short duration of immunity after vaccination which contrasts with prolonged immunity after natural infection. Here we show by laser capture microdissection in combination with quantitative real-time reverse transcription polymerase chain reaction, immunohistochemical analysis and corroborate by in situ hybridization that FMDV locates rapidly to, and is maintained in, the light zone of germinal centres following primary infection of naïve cattle. We propose that maintenance of non-replicating FMDV in these sites represents a source of persisting infectious virus and also contributes to the generation of long-lasting antibody responses against neutralising epitopes of the virus

Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity

Laboratory animal models have provided valuable insight into foot-and-mouth disease virus (FMDV) pathogenesis in epidemiologically important target species. While not perfect, these models have delivered an accelerated time frame to characterize the immune responses in natural hosts and a platform to evaluate therapeutics and vaccine candidates at a reduced cost. Further expansion of these models in mice has allowed access to genetic mutations not available for target species, providing a powerful and versatile experimental system to interrogate the immune response to FMDV and to target more expensive studies in natural hosts. The purpose of this review is to describe commonly used FMDV infection models in laboratory animals and to cite examples of when these models have failed or successfully provided insight relevant for target species, with an emphasis on natural and vaccine-induced immunity

Appendix 53 DEFINING THE PERIOD OF INFECTIOUSNESS IN CATTLE NATURALLY INFECTED WITH FOOT-AND-MOUTH DISEASE VIRUS

ABSTRACT Objectives To broaden our understanding of FMDV transmission in cattle; quantify variability in infectiousness at different time points and establish the peak of infectiousness; pin-point predictors of infectiousness and provide accurate data for mathematical modelling of FMD. Materials and methods For each of four experiments, two naïve animals were inoculated intradermolingually with O UKG 34/2001 and two days post inoculation used to directly challenge two further naïve cattle for 24 hrs. At different days post challenge these direct contact challenged 'donors' were used to challenge the remaining naïve animals (recipients) either by direct or indirect contact, which were clinically monitored and sampled for 14 days. Clinical assessment included rectal temperature and detailed scoring of clinical signs. Samples included oropharyngeal and nasal fluid, and blood, and air samples, taken pre-and at challenge and assayed for the presence of virus. Results All 'donors' developed clinical signs of FMD, although the incubation period to onset of clinical signs varied between 2 and 8 days post challenge. Transmission only occurred by direct contact (8 transmission events out of 28 challenges) and the incubation period similarly varied between 2 and 8 days. Significant amounts of infectious virus were recovered from air samples during challenge. Virus was recovered from all donors and clinically diseased 'recipients'. Discussion Infected cattle were shown to be infectious up to a maximum of 4 days. However, estimates indicate a range of values (42.53 to 87.97 hours) for the duration of the infectious period, with an average of 61.85 hours. A good indicator of infectiousness is the presence of lesions in the oral cavity, mouth, tongue or snout. No transmission was evident by indirect contact which indicates that airborne transmission may not readily occur between cattle. OBJECTIVES: After an initial pilot study, four animal experiments were performed to broaden our understanding of FMDV transmission between individual cattle. Further inferences to within herd or 'over the fence' transmission could be made with subsequent quantification of variability in infectiousness at different time points, and establishing the peak of infectiousness. Using clinical data we aimed to identify and pin-point the predictors of infectiousness in cattle. These will be used to provide further data for the mathematical modellers, to further clarify the window of infectiousness in cattle and effect of prophylactic intervention. MATERIALS AND METHOD

Chimeric O1K foot-and-mouth disease virus with SAT2 outer capsid as an FMD vaccine candidate

Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth disease (FMD). FMD outbreaks have severe economic impact due to production losses and associated control measures. FMDV is found as seven distinct serotypes, but there are numerous subtypes within each serotype, and effective vaccines must match the subtypes circulating in the field. In addition, the O and Southern African Territories (SAT) serotypes, are relatively more thermolabile and their viral capsids readily dissociate into non-immunogenic pentameric subunits, which can compromise the effectiveness of FMD vaccines. Here we report the construction of a chimeric clone between the SAT2 and O serotypes, designed to have SAT2 antigenicity. Characterisation of the chimeric virus showed growth kinetics equal to that of the wild type SAT2 virus with better thermostability, attributable to changes in the VP4 structural protein. Sequence and structural analyses confirmed that no changes from SAT2 were present elsewhere in the capsid as a consequence of the VP4 changes. Following exposure to an elevated temperature the thermostable SAT2-O1K chimera induced higher neutralizing-antibody titres in comparison to wild type SAT2 virus.</p

Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007.

Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes