title: Ovine immune parameters following immunisation against Mycobacterium avium ssp. paratuberculosis using a lipid-based live-cell vaccine.
abstract: Current commercial sheep vaccines against Mycobacterium avium subspecies paratuberculosis (MAP) are based on the use of live or killed cells from avirulent MAP strains. These stimulate a mixed immune response, featuring both antibody-based and cell-mediated immunity, and can only confer partial protection against Johne's disease but do not prevent infection. This study aimed to identify immune responses in sheep following immunisation with a novel lipid-based live-cell vaccine, drawing comparisons against responses observed to a commercial killed-cell vaccine (Gudair). The live vaccine was administered either subcutaneously or intra-peritoneally, as either a single-dose vaccine or in an homologous prime-boost protocol. A single-dose of the live vaccine was found to stimulate a cellular immune response similar to that of single-dose Gudair, but with markedly lower levels of antibody; however, homologous boosting with the live vaccine, by either s.c. or i.p. routes, generated higher levels of MAP-specific antibody. All immunisation regimes tended to decrease the proportion of CD4(+) T cells but increase the proportions of gammadeltaTCR(+) T cells and CD25(+) cells in antigen-stimulated ex vivo blood samples. The CD8(+):gammadeltaTCR(+) T cell ratio, thought to represent a reduced regulatory capacity among T cells responding to MAP, was increased among animals receiving either Gudair or a single i.p. dose of the live vaccine; however, only the Gudair vaccine simultaneously increased the level of lymph node IFNgamma mRNA expression, and this treatment also caused a significant elevation in the IFNgamma:IL-10 (effector:regulatory) cytokine expression ratio. Thus, among these immunisation regimes, the responses generated by a single s.c. dose of the novel live-cell vaccine appeared to selectively target the CMI-based immune profile thought necessary for control of MAP infection; in contrast, homologous prime-boosting with the live vaccine stimulated a mixed immune response similar to that produced by immunisation with Gudair.
authors.affiliation: Disease Research Laboratory, Department of Microbiology & Immunology, University of Otago, Dunedin, New Zealand.
authors.forename: Sonia
authors.initials: S
authors.lastname: Gillan
authors.forename: Alan D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Rory
authors.initials: R
authors.lastname: O'Brien
authors.forename: J Frank T
authors.initials: JF
authors.lastname: Griffin
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D007114:Immunization; D016130:Immunophenotyping; D008055:Lipids / Q000008:administration & dosage; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D008055:Lipids; D012333:RNA, Messenger