Superior Protection from Live-Attenuated Vaccines Directed Against Johne's Disease

Overview

Journal Clin Vaccine Immunol

Publisher American Society for Microbiology

Specialties Allergy & Immunology
Pathology

Date 2016 Nov 4

PMID 27806993

Citations 14

Authors

Daniel C Shippy

Justin J Lemke

Aubrey Berry

Kathryn Nelson

Murray E Hines 2nd

Adel M Talaat

Affiliations

Soon will be listed here.

Abstract

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the etiological agent of Johne's disease in ruminants. Johne's disease is an important enteric infection causing large economic losses associated with infected herds. In an attempt to fight this infection, we created two novel live-attenuated vaccine candidates with mutations in sigH and lipN (pgsH and pgsN, respectively). Earlier reports in mice suggested these vaccines are promising candidates to fight Johne's disease in ruminants. In this study, we tested the performances of the two constructs as vaccine candidates using the goat model of Johne's disease. Both vaccines appeared to provide significant immunity to goats against challenge from wild-type M. paratuberculosis The pgsH and pgsN constructs showed a significant reduction in histopathological lesions and tissue colonization compared to nonvaccinated goats and those vaccinated with an inactivated vaccine. Unlike the inactivated vaccine, the pgsN construct was able to eliminate fecal shedding from challenged animals, a feature that is highly desirable to control Johne's disease in infected herds. Furthermore, strong initial cell-mediated immune responses were elicited in goats vaccinated with pgsN that were not demonstrated in other vaccine groups. Overall, the results indicate the potential use of live-attenuated vaccines to control intracellular pathogens, including M. paratuberculosis, and warrant further testing in cattle, the main target for Johne's disease control programs.

Citing Articles

design of a multi-epitope vaccine against subspecies .

Guo W, Wang X, Hu J, Zhang B, Zhao L, Zhang G Front Immunol. 2025; 16:1505313.

PMID: 39935480 PMC: 11810964. DOI: 10.3389/fimmu.2025.1505313.

Evaluation of alternative vaccination routes against paratuberculosis in goats.

Criado M, Silva M, Arteche-Villasol N, Zapico D, Elguezabal N, Molina E Front Vet Sci. 2024; 11:1457849.

PMID: 39664904 PMC: 11631874. DOI: 10.3389/fvets.2024.1457849.

Immunogenicity and efficacy of an oral live-attenuated vaccine for bovine Johne's disease.

Eshraghisamani R, Facciuolo A, Harman-McKenna V, Illanes O, De Buck J Front Immunol. 2024; 14:1307621.

PMID: 38283338 PMC: 10810994. DOI: 10.3389/fimmu.2023.1307621.

Immuno-reactivity evaluation of Mce-truncated subunit candidate vaccine against Mycobacterium avium subspecies paratuberculosis challenge in the goat models.

Haghkhah M, Hemati Z, Derakhshandeh A, Namazi F, Chaubey K, Singh S BMC Vet Res. 2023; 19(1):157.

PMID: 37710242 PMC: 10500891. DOI: 10.1186/s12917-023-03715-z.

Evaluation of subsp. isocitrate lyase () and ABC transporter () knockout mutants as vaccine candidates.

Eshraghisamani R, Arrazuria R, Luo L, De Buck J Front Cell Infect Microbiol. 2023; 13:1149419.

PMID: 37065210 PMC: 10098363. DOI: 10.3389/fcimb.2023.1149419.

References

Park K, Allen A, Barrington G, Davis W . Deletion of relA abrogates the capacity of Mycobacterium avium paratuberculosis to establish an infection in calves. Front Cell Infect Microbiol. 2014; 4:64. PMC: 4030200. DOI: 10.3389/fcimb.2014.00064. View

Knust B, Patton E, Ribeiro-Lima J, Bohn J, Wells S . Evaluation of the effects of a killed whole-cell vaccine against Mycobacterium avium subsp paratuberculosis in 3 herds of dairy cattle with natural exposure to the organism. J Am Vet Med Assoc. 2013; 242(5):663-9. DOI: 10.2460/javma.242.5.663. View

Sechi L, Scanu A, Molicotti P, Cannas S, Mura M, Dettori G . Detection and Isolation of Mycobacterium avium subspecies paratuberculosis from intestinal mucosal biopsies of patients with and without Crohn's disease in Sardinia. Am J Gastroenterol. 2005; 100(7):1529-36. DOI: 10.1111/j.1572-0241.2005.41415.x. View

Stabel J . Cytokine secretion by peripheral blood mononuclear cells from cows infected with Mycobacterium paratuberculosis. Am J Vet Res. 2000; 61(7):754-60. DOI: 10.2460/ajvr.2000.61.754. View

Shin S, Wu C, Steinberg H, Talaat A . Identification of novel virulence determinants in Mycobacterium paratuberculosis by screening a library of insertional mutants. Infect Immun. 2006; 74(7):3825-33. PMC: 1489745. DOI: 10.1128/IAI.01742-05. View

Kalis C, Hesselink J, Barkema H, Collins M . Use of long-term vaccination with a killed vaccine to prevent fecal shedding of Mycobacterium avium subsp paratuberculosis in dairy herds. Am J Vet Res. 2001; 62(2):270-4. DOI: 10.2460/ajvr.2001.62.270. View

Ghosh P, Hsu C, Alyamani E, Shehata M, Al-Dubaib M, Al-Naeem A . Genome-wide analysis of the emerging infection with Mycobacterium avium subspecies paratuberculosis in the Arabian camels (Camelus dromedarius). PLoS One. 2012; 7(2):e31947. PMC: 3290536. DOI: 10.1371/journal.pone.0031947. View

Tewari D, Hovingh E, Linscott R, Martel E, Lawrence J, Wolfgang D . Mycobacterium avium subsp. paratuberculosis antibody response, fecal shedding, and antibody cross-reactivity to Mycobacterium bovis in M. avium subsp. paratuberculosis-infected cattle herds vaccinated against Johne's disease. Clin Vaccine Immunol. 2014; 21(5):698-703. PMC: 4018888. DOI: 10.1128/CVI.00032-14. View

Windsor P, Eppleston J, Dhand N, Whittington R . Effectiveness of Gudair™ vaccine for the control of ovine Johne's disease in flocks vaccinating for at least 5 years. Aust Vet J. 2014; 92(7):263-8. DOI: 10.1111/avj.12194. View

10.

Lombard J, Gardner I, Jafarzadeh S, Fossler C, Harris B, Capsel R . Herd-level prevalence of Mycobacterium avium subsp. paratuberculosis infection in United States dairy herds in 2007. Prev Vet Med. 2012; 108(2-3):234-8. DOI: 10.1016/j.prevetmed.2012.08.006. View

11.

Wu C, Glasner J, Collins M, Naser S, Talaat A . Whole-genome plasticity among Mycobacterium avium subspecies: insights from comparative genomic hybridizations. J Bacteriol. 2005; 188(2):711-23. PMC: 1347307. DOI: 10.1128/JB.188.2.711-723.2006. View

12.

Klawonn W, Cussler K, Drager K, Gyra H, Kohler H, Zimmer K . [The importance of allergic skin test with Johnin, antibody ELISA, cultural fecal test as well as vaccination for the sanitation of three chronically paratuberculosis-infected dairy herds in Rhineland-Palatinate]. Dtsch Tierarztl Wochenschr. 2003; 109(12):510-6. View

13.

Ghosh P, Wu C, Talaat A . Key role for the alternative sigma factor, SigH, in the intracellular life of Mycobacterium avium subsp. paratuberculosis during macrophage stress. Infect Immun. 2013; 81(6):2242-57. PMC: 3676012. DOI: 10.1128/IAI.01273-12. View

14.

Park K, Allen A, Bannantine J, Seo K, Hamilton M, Abdellrazeq G . Evaluation of two mutants of Mycobacterium avium subsp. paratuberculosis as candidates for a live attenuated vaccine for Johne's disease. Vaccine. 2011; 29(29-30):4709-19. PMC: 3114198. DOI: 10.1016/j.vaccine.2011.04.090. View

15.

Uzonna J, Chilton P, Whitlock R, Habecker P, Scott P, Sweeney R . Efficacy of commercial and field-strain Mycobacterium paratuberculosis vaccinations with recombinant IL-12 in a bovine experimental infection model. Vaccine. 2003; 21(23):3101-9. DOI: 10.1016/s0264-410x(03)00261-5. View

16.

Losinger W . Economic impact of reduced milk production associated with Johne's disease on dairy operations in the USA. J Dairy Res. 2005; 72(4):425-32. DOI: 10.1017/S0022029905001007. View

17.

Muskens J, VAN Zijderveld F, Eger A, Bakker D . Evaluation of the long-term immune response in cattle after vaccination against paratuberculosis in two Dutch dairy herds. Vet Microbiol. 2002; 86(3):269-78. DOI: 10.1016/s0378-1135(02)00006-8. View

18.

OGarra A, Redford P, McNab F, Bloom C, Wilkinson R, Berry M . The immune response in tuberculosis. Annu Rev Immunol. 2013; 31:475-527. DOI: 10.1146/annurev-immunol-032712-095939. View

19.

Stringer L, Wilson P, Heuer C, Mackintosh C . A randomised controlled trial of Silirum vaccine for control of paratuberculosis in farmed red deer. Vet Rec. 2013; 173(22):551. DOI: 10.1136/vr.101799. View

20.

Naser S, Ghobrial G, Romero C, Valentine J . Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn's disease. Lancet. 2004; 364(9439):1039-44. DOI: 10.1016/S0140-6736(04)17058-X. View