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Immunity, safety and protection of an Adenovirus 5 prime--Modified Vaccinia virus Ankara boost subunit vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves.

Bull, TJ; Vrettou, C; Linedale, R; McGuinnes, C; Strain, S; McNair, J; Gilbert, SC; Hope, JC (2014) Immunity, safety and protection of an Adenovirus 5 prime--Modified Vaccinia virus Ankara boost subunit vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves. Veterinary Research, 45 (1). ISSN 1297-9716 https://doi.org/10.1186/s13567-014-0112-9
SGUL Authors: Bull, Timothy John

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Abstract

Vaccination is the most cost effective control measure for Johne's disease caused by Mycobacterium avium subspecies paratuberculosis (MAP) but currently available whole cell killed formulations have limited efficacy and are incompatible with the diagnosis of bovine tuberculosis by tuberculin skin test. We have evaluated the utility of a viral delivery regimen of non-replicative human Adenovirus 5 and Modified Vaccinia virus Ankara recombinant for early entry MAP specific antigens (HAV) to show protection against challenge in a calf model and extensively screened for differential immunological markers associated with protection. We have shown that HAV vaccination was well tolerated, could be detected using a differentiation of infected and vaccinated animals (DIVA) test, showed no cross-reactivity with tuberculin and provided a degree of protection against challenge evidenced by a lack of faecal shedding in vaccinated animals that persisted throughout the 7 month infection period. Calves given HAV vaccination had significant priming and boosting of MAP derived antigen (PPD-J) specific CD4+, CD8+ IFN-γ producing T-cell populations and, upon challenge, developed early specific Th17 related immune responses, enhanced IFN-γ responses and retained a high MAP killing capacity in blood. During later phases post MAP challenge, PPD-J antigen specific IFN-γ and Th17 responses in HAV vaccinated animals corresponded with improvements in peripheral bacteraemia. By contrast a lack of IFN-γ, induction of FoxP3+ T cells and increased IL-1β and IL-10 secretion were indicative of progressive infection in Sham vaccinated animals. We conclude that HAV vaccination shows excellent promise as a new tool for improving control of MAP infection in cattle.

Item Type: Article
Additional Information: © 2014 Bull et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Veterinary Sciences, 0605 Microbiology, 0707 Veterinary Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Veterinary Research
Article Number: 112
ISSN: 1297-9716
Language: eng
Dates:
DateEvent
29 October 2014Published
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
BB/H010556/1Biotechnology and Biological Sciences Research CouncilUNSPECIFIED
BB/H010718/1Biotechnology and Biological Sciences Research CouncilUNSPECIFIED
PubMed ID: 25480162
Web of Science ID: WOS:000345960800001
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/107359
Publisher's version: https://doi.org/10.1186/s13567-014-0112-9

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