title: Efficacy of novel lipid-formulated whole bacterial cell vaccines against Mycobacterium avium subsp. paratuberculosis in sheep.
abstract: Mycobacterium avium subsp. paratuberculosis [MAP], the causative agent of enteric Johne's disease, incurs significant economic losses to the livestock industry. Prophylactic vaccination can be employed as a control means, however mineral oil-based vaccines currently in practice have limited efficacy, produce strong antibody responses that confound serological diagnostic testing, and cause severe injection site reactions. In the present study, the safety and efficacy of a commercial mineral oil-adjuvanted vaccine (Gudair) was compared with novel parenteral-route vaccines in sheep; these comprised live or heat-killed (HK) whole cell preparations of MAP strain 316F, formulated into a food-grade lipid vaccine delivery matrix. Subcutaneous administration of lipid-formulated live or HK 316F-induced significantly fewer adverse injection site reactions than Gudair; adverse injection site reactions were eliminated altogether by intraperitoneal (i.p.) injection of lipid-formulated live 316F. Injections of lipid-formulated 316F-induced significant peripheral blood cell-mediated immune (CMI) responses in the absence of antibody, while Gudair-induced strong antibody and CMI reactivity. Vaccinated and non-vaccinated control sheep were challenged via oral inoculation of a virulent MAP isolate, and disease progress was monitored for 16 months, followed by necropsy. All vaccine regimes reduced the overall pathological grading of biopsied intestinal tract (IT) tissues; among these, only Gudair promoted a significant reduction in the incidence of histopathological IT lesions, while only i.p. injection of lipid-formulated live 316F significantly reduced the incidence of gross IT lesions. All lipid-formulated vaccines (but not Gudair) significantly reduced the incidence of bacteriological culture-confirmed MAP infection. This study identifies a new vaccination strategy against Johne's disease in sheep using conventional MAP vaccine strains formulated in a metabolisable lipid delivery matrix.
authors.affiliation: Department of Microbiology & Immunology, University of Otago, Dunedin, New Zealand. frank.griffin@stonebow.otago.ac.nz
authors.forename: J Frank T
authors.initials: JF
authors.lastname: Griffin
authors.forename: Alan D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Simon
authors.initials: S
authors.lastname: Liggett
authors.forename: Philip A
authors.initials: PA
authors.lastname: Farquhar
authors.forename: Colin G
authors.initials: CG
authors.lastname: Mackintosh
authors.forename: Douwe
authors.initials: D
authors.lastname: Bakker
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D001835:Body Weight; D041981:Gastrointestinal Tract / Q000473:pathology; D007372:Interferons / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008899:Mineral Oil / Q000494:pharmacology*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010283:Paratuberculosis / Q000517:prevention & control*; D012720:Severity of Illness Index; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D008899:Mineral Oil; D007372:Interferons