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Bluetongue vaccines in Europe

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The article reviews the history, present status and the future of BT vaccines in Europe. So far, an attenuated (modified live viruses, MLV) and inactivated virus vaccines against BT were developed and used in the field. Moreover, the virus-like particles (VLPs) produced from recombinant baculovirus, and live recombinant vaccinia or canarypox virus-vectored vaccines were tested in the laboratory. The main aims of BT vaccination strategy are: to prevent clinical disease, to reduce the spread of the BTV in the environment and to protect movement of susceptible animals between affected and free zones. Actually, all of the most recent European BT vaccination campaigns have used exclusively inactivated vaccines. The use of inactivated vaccines avoid risk associated with the use of live-attenuated vaccines, such as reversion to virulence, reassortment of genes with field strain, teratogenicity and insufficient attenuation leading to clinical disease. The mass vaccinations of all susceptible animals are the most efficient veterinary method to fight against BT and successful control of disease. The vaccination of livestock has had a major role in reducing BTV circulation and even in eradicating the virus from most areas of Europe.
Climate changes may have significant impact on animal health, including changes in the distribution and seasonality of vector-borne diseases. Arboviruses, such as bluetongue virus (BTV), are particularly susceptible to climate change because of their small size and their ability to adapt to variations in the temperature of the environment. Climate also has long-term indirect effects on the transmission of BT via its effects on the distribution and availability of suitable habitats. Changes in BT incidence in Europe have been matched by spatio-temporal changes in regional climates, including the specific climatic drivers of BTV infection. The climate changes are responsible for the occurrence and distribution of BT through their impact on the viral vectors. Changes in climate, i.e. temperature, precipitation, humidity, wind, etc., can influence various aspects of the Culicoides vectors’ life cycle, including survival, population numbers, vector-pathogen interactions, pathogen replication, vector behaviour and, of course, its distribution. Different species of Culicoides have different environmental tolerances, and the optimal temperature and humidity levels for populations of Afro-Asiatic species, such as C. imicola, are different from those for Palearctic species, such as the C. obsoletus and C. pulicaris groups. However, the biotic processes of changing vector roles and distribution have been as important as the climatic process in driving the invasion of Europe by multiple BTV strains. The enhanced transmission of BTV by indigenous European vectors has been instrumental in the spread and persistence of infection in cooler and wetter areas of different regions of Europe after the invasion. The vectorial capacity of Culicoides is dynamic and climate-mediated, making it difficult to state unequivocally that particular species cannot or will not be involved in transmission – even of strains that enter Europe unexpectedly from geographically remote regions.
Understanding the interaction between the bluetongue virus (BTV), the Culicoides vector and the ruminant host is essential to control bluetongue (BT). This triangle of interaction can be understood individually at the level of the virus, the level of vector and the host level. BTV-vector-host interactions involve physiological and ecological mechanisms, and they have evolved under a specific set of environmental conditions. Recent advances in understanding this interaction include increased knowledge of the virus replication cycle, BTV immunology and pathogenesis in the vertebrate host, as well as the virulence and pathogenicity features of newly discovered BTV serotypes. To understand the virus-host-vector interaction, new molecular biology techniques and experimental infection biology methods have been widely used. The next-generation sequencing, the establishment of a reverse genetics system for the virus, and development of novel infection models and refinement of the existing BTV experimental infection methodologies have proven very helpful. This progress in biotechnology has also made it possible to develop new-generation BTV vaccines, such as disabled infectious single cycle (DISC) vaccines and disabled infectious single animal (DISA) vaccines. However, several questions still need to be answered, such as those concerning cellular pathways involved in the induction of innate immunity and the function of NS4 in the BTV replication cycle. In addition, the identities of specific molecular determinants and the role of quasi-species diversity in determining BTV phenotype are still unclear and should be better explained.
The aim of this study was to determine the diagnostic specificity, sensitivity and repeatability of four commercially available ELISA kits for the detection of antibodies against bluetongue (BT) virus. The relative specificity of ELISAs was estimated using a panel of sera originated from healthy cattle never vaccinated nor exposed to BT virus. All ELISA kits had a high relative specificity (99.2-99.4%). The relative sensitivity of ELISAs estimated using a panel of sera collected from BTV infected cattle was also high and similar for all kits (97.4-100%). However, the relative sensitivity evaluated on the basis of testing of vaccinated animals was different for the used ELISAs: the LSI, ID VET and Ingenasa kits had a high sensitivity (85.2-98.2%) but the sensitivity of VMRD ELISA was much lower (68.6%). The repeatability of ELISAs was expressed as a coefficient of variation (CV) of results of sera tested 5 times in the same day and 10 times in different days through the period of 2 months, by the same person, in the same conditions, and by using of the same equipment. The CVs of sera tested in Ingenasa and ID VET kits ranged from 6.1 to 9.8% and were below the 10% threshold adopted as a maximal for the acceptable repeatability of a method. In conclusion, it can be stated that the applied ELISAs can be a valuable diagnostic tool for the serological monitoring studies in the BTV infected premises. Nevertheless, the Ingenasa and ID VET ELISAs can be the most useful in sero- -surveillance of livestock following vaccination.
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