title: Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines.
abstract: Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV.
  
  
  OBJECTIVE
  Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new approaches to produce highly attenuated, safer vaccines was evident after the development of the BTV reverse-genetics system that allows the introduction of targeted mutations in the virus genome. We targeted an essential gene to develop disabled virus strains as vaccine candidates. The results presented in this report further substantiate our previous evidence and support the suitability of these virus strains as the next-generation BTV vaccines.
authors: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Cristina C
authors: CC
authors: Celma
authors: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Meredith
authors: M
authors: Stewart
authors: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
authors: Kerstin
authors: K
authors: Wernike
authors: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
authors: Michael
authors: M
authors: Eschbaumer
authors: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Lorenzo
authors: L
authors: Gonzalez-Molleda
authors: Université Paris-Est ANSES Alfort, UMR 1161 ANSES/INRA/ENVA, Maisons-Alfort, France.
authors: Emmanuel
authors: E
authors: Breard
authors: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
authors: Claudia
authors: C
authors: Schulz
authors: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
authors: Bernd
authors: B
authors: Hoffmann
authors: Unit Vesicular and Exotic Diseases, CODA-CERVA, Uccle, Belgium.
authors: Andy
authors: A
authors: Haegeman
authors: Unit Vesicular and Exotic Diseases, CODA-CERVA, Uccle, Belgium.
authors: Kris
authors: K
authors: De Clercq
authors: Université Paris-Est ANSES Alfort, UMR 1161 ANSES/INRA/ENVA, Maisons-Alfort, France.
authors: Stephan
authors: S
authors: Zientara
authors: Central Veterinary Institute of Wageningen University, Wageningen, The Netherlands.|Department of Biochemistry, North-West University, Potchefstroom, South Africa.
authors: Piet A
authors: PA
authors: van Rijn
authors: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Insel Riems, Germany.
authors: Martin
authors: M
authors: Beer
authors: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom polly.roy@lshtm.ac.uk.
authors: Polly
authors: P
authors: Roy
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001483:Base Sequence; D001819:Bluetongue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D001820:Bluetongue virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002417:Cattle; D002460:Cell Line; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D008297:Male; D059386:Reverse Genetics; D065288:Serogroup; D012756:Sheep; D014611:Vaccination; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit; D014765:Viral Vaccines / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit; D014765:Viral Vaccines
keywords: Next-generation vaccine; bluetongue virus; reverse genetics