ArticleVaccine2011
Evaluation of two mutants of Mycobacterium avium subsp. paratuberculosis as candidates for a live attenuated vaccine for Johne's disease.
Article in Vaccine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 85 citations in OpenAlex.
- Functional analysis of the intracellular survival ofJournal of bacteriology · 2025Article
- The anti-inflammatory effect of a magnoliae cortex and Zea mays L. extract mixture in a canine model of ligature-induced periodontitis.BMC veterinary research · 2024Article
- The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line.BMC genomic data · 2024Article
- Use of RNA-seq to identify genes encoding cytokines and chemokines activated following uptake and processing a candidate peptide vaccine developed againstBrazilian journal of veterinary medicine · 2024Article
- Evaluation of alternative vaccination routes against paratuberculosis in goats.Frontiers in veterinary science · 2024Article
- Vaccines for immune tolerance against autoimmune disease.Advanced drug delivery reviews · 2023Review
- Modeling Paratuberculosis in Laboratory Animals, Cells, or Tissues: A Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines, and Therapy Studies.Animals : an open access journal from MDPI · 2023Review
- Assessment of Tuberculosis Biomarkers in Paratuberculosis-infected Cattle.Journal of veterinary research · 2023Article
- Evaluation ofFrontiers in cellular and infection microbiology · 2023Article
- Immunogenicity and efficacy of an oral live-attenuated vaccine for bovine Johne's disease.Frontiers in immunology · 2023Article
- Review
- Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats.Frontiers in veterinary science · 2022Article
- Identification of essential genes inFrontiers in microbiology · 2022Article
- Advances in Understanding of the Immune Response to Mycobacterial Pathogens and Vaccines through Use of Cattle andVaccines · 2021Review
- A Protective Vaccine against Johne's Disease in Cattle.Microorganisms · 2020Article
- A Bovine EntericFrontiers in immunology · 2020Article
- Vaccine approaches for the 'therapeutic management' ofThe veterinary quarterly · 2019Review
- Capacity to Elicit Cytotoxic CD8 T Cell Activity AgainstFrontiers in immunology · 2019Article
- A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa major membrane protein elicit development of cytotoxic T lymphocytes with ability to kill intracellular bacteria.Veterinary research · 2018Article
- Protein Kinase G Induces an Immune Response in Cows Exposed toBioMed research international · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Control of Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis, has been difficult because of a lack of an effective vaccine. To address this problem we used targeted gene disruption to develop candidate mutants with impaired capacity to survive ex vivo and in vivo to test as a vaccine. We selected relA and pknG, genes known to be important virulence factors in Mycobacterium tuberculosis and Mycobacterium bovis, for initial studies. Deletion mutants were made in a wild type Map (K10) and its recombinant strain expressing the green fluorescent protein (K10-GFP). Comparison of survival in an ex vivo assay revealed deletion of either gene attenuated survival in monocyte-derived macrophages compared to survival of wild-type K10. In contrast, study in calves revealed survival in vivo was mainly affected by deletion of relA. Bacteria were detected in tissues from wild-type and the pknG mutant infected calves by bacterial culture and PCR at three months post infection. No bacteria were detected in tissues from calves infected with the relA mutant (P<0.05). Flow cytometric analysis of the immune response to the wild-type K10-GFP and the mutant strains showed deletion of either gene did not affect their capacity to elicit a strong proliferative response to soluble antigen extract or live Map. Quantitative RT-PCR revealed genes encoding IFN-γ, IL-17, IL-22, T-bet, RORC, and granulysin were up-regulated in PBMC stimulated with live Map three months post infection compared to the response of PBMC pre-infection. A challenge study in kid goats showed deletion of pknG did not interfere with establishment of an infection. As in calves, deletion of relA attenuated survival in vivo. The mutant also elicited an immune response that limited colonization by challenge wild type Map. The findings show the relA mutant is a good candidate for development of a live attenuated vaccine for Johne's disease.
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