title: CD4⁺ T-cells, γδ T-cells and B-cells are associated with lack of vaccine protection in Mycobacterium avium subspecies paratuberculosis infection.
abstract: Vaccination is one of the strategies used to control the spread of Mycobacterium avium subspecies paratuberculosis (MAP) infection in livestock. Gudair(®) is a widely-used vaccine in sheep and goats and is the only vaccine approved for use in sheep in Australia and New Zealand. This vaccine reduces mortality due to MAP-infection by up to 90% but some sheep remain infectious by shedding MAP in faeces, despite vaccination. In this study, using an experimental infection model in sheep, our aim was to assess differences in immune parameters between vaccinated MAP-exposed sheep in which the vaccine was effective compared to those in which it failed to protect against infection. We assessed immune parameters such as MAP-specific IFNγ, IL-10 and lymphocyte proliferative responses and serum antibody levels. At the end of the trial, 72% of non-vaccinated sheep and 24% of vaccinated sheep were infected, as defined by the detection of viable MAP in intestinal tissues when the trial was terminated at 49 weeks post exposure. There were significant differences in the proliferation of CD4(+), B and γδ T-cells over time in vaccinated sheep in which the vaccine failed to protect against infection compared to the non-infected vaccinated sheep. There were no significant differences in the IFNγ response or serum antibody levels between the vaccinated infected and vaccinated non-infected sheep. These results emphasise the importance of specific lymphocyte subsets in protecting against MAP-infection, especially in vaccinated sheep, and that immune parameters other than the commonly used IFNγ and antibody tests are required when assessing vaccine efficacy.
authors.affiliation: Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia. Electronic address: kumi.desilva@sydney.edu.au.
authors.forename: Kumudika
authors.initials: K
authors.lastname: de Silva
authors.affiliation: Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Karren
authors.initials: K
authors.lastname: M Plain
authors.affiliation: Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Douglas
authors.initials: D
authors.lastname: J Begg
authors.affiliation: Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Auriol
authors.initials: A
authors.lastname: C Purdie
authors.affiliation: Faculty of Veterinary Science, University of Sydney, 425 Werombi Road, Camden 2570, NSW, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: J Whittington
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001315:Australia; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D007371:Interferon-gamma / Q000378:metabolism; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D009520:New Zealand; D010283:Paratuberculosis / Q000276:immunology / Q000517:prevention & control*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D012756:Sheep; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D017211:Treatment Failure; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014436:Typhoid-Paratyphoid Vaccines; D007371:Interferon-gamma
keywords: Cell mediated immune response; Gudair vaccine; Johne's disease; Sheep; Vaccine non-response