title: Immunization of bighorn sheep against Mannheimia haemolytica with a bovine herpesvirus 1-vectored vaccine.
abstract: Mannheimia haemolytica is an important pathogen of pneumonia in bighorn sheep (BHS), consistently causing 100% mortality under experimental conditions. Leukotoxin is the critical virulence factor of M. haemolytica. In a 'proof of concept' study, a vaccine containing leukotoxin and surface antigens of M. haemolytica induced 100% protection in BHS, but required multiple booster doses. Vaccination of wildlife is difficult. BHS, however, can be vaccinated at the time of transplantation, but administration of booster doses is impossible. A vaccine that does not require booster doses, therefore, is ideal for vaccination of BHS. Herpesviruses are ideal vectors for development of such a vaccine because of their ability to undergo latency with subsequent reactivation which obviates the need for booster administration. The objective of this study was to evaluate the potential of bovine herpesvirus 1 (BHV-1) as a vector encoding M. haemolytica immunogens. As the first step towards this goal, the permissiveness of BHS for BHV-1 infection was determined. BHS inoculated with wild-type BHV-1 shed the virus following infection. The lytic phase of infection was superseded by latency, and treatment of latently-infected BHS with dexamethasone reactivated the virus. A recombinant BHV-1-vectored vaccine encoding a leukotoxin-neutralizing epitope and an immuno-dominant epitope of the outer membrane protein PlpE was developed by replacing the viral glycoprotein C gene with a leukotoxin-plpE chimeric gene. Four of six BHS vaccinated with the recombinant virus developed significant leukotoxin-neutralizing antibodies at day 21 post-vaccination, while two of six BHS developed significant surface antigen antibodies at day 17 post-vaccination. These antibodies, however, were inadequate for protection of BHS against M. haemolytica challenge. These data indicate that BHV-1 is a suitable vector for immunization of BHS, but additional experimentation with the chimeric insert is necessary for development of a more efficacious vaccine.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA.
authors.forename: Sai A
authors.initials: SA
authors.lastname: Batra
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA.
authors.forename: Sudarvili
authors.initials: S
authors.lastname: Shanthalingam
authors.affiliation: Department of Medical-Veterinary Science, University of Parma, Parma, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA; Washington Animal Disease Diagnostic Laboratory, Washington State University, Pullman, WA, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Haldorson
authors.affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA, USA.
authors.forename: Shafiqul
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA; Animal Disease Research Unit, Agricultural Research Service, Department of Agriculture, Pullman, WA, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: White
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA. Electronic address: ssrikumaran@vetmed.wsu.edu.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Srikumaran
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D004337:Drug Carriers; D005822:Genetic Vectors; D007242:Herpesvirus 1, Bovine / Q000235:genetics* / Q000502:physiology; D016978:Mannheimia haemolytica / Q000276:immunology*; D012766:Pasteurellosis, Pneumonic / Q000517:prevention & control*; D012756:Sheep; D012757:Sheep Diseases / Q000517:prevention & control*; D034581:Sheep, Bighorn; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D001428:Bacterial Vaccines; D004337:Drug Carriers; D014614:Vaccines, Synthetic
keywords: Bighorn sheep; Bovine herpesvirus 1; Mannheimia haemolytica; Vaccine; Vector