Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

Abstract

Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

Virulence and Immunity Orchestrated by the Global Gene Regulator sigL in Mycobacterium avium subsp. paratuberculosis

“…paratuberculosis ⌬ppiA), defective in the peptidyl-prolyl cis-trans-isomerase, showed a mild attenuated phenotype relative to the wild-type strain and resulted in limited tissue colonization following challenge with parental M. avium subsp. paratuberculosis strain (53). Alternatively, the attenuated M. avium subsp.…”

“…paratuberculosis mutants (e.g., WAg915 and M. avium subsp. paratuberculosis ⌬leuD) as live attenuated vaccine candidates in the murine model of paratuberculosis (53,54). The mutant strain WAg915 (M. avium subsp.…”

Evaluation of a Mycobacterium avium subsp. paratuberculosisleuDMutant as a Vaccine Candidate against Challenge in a Caprine Model

“…Several attempts have been made to successfully produce mutant strains of M. avium subsp. paratuberculosis with vaccine potential by exploiting transposon mutagenesis and allelic exchange (17)(18)(19). The latter technology affords a method to select genes associated with virulence or function for gene disruption.…”

Therapeutic Potential of a Candidate relA Deletion Mutant Vaccine of Mycobacterium Avium Subsp. Paratuberculosis

“…paratuberculosis (Map) that induces sterile immunity against Johne's disease (JD) or prevents disease progression. These approaches have included development of killed whole vaccines, live attenuated, DNA and subunit vaccines and tests in different animal species (Bull et al 2007;Park et al 2008;Juste et al 2009;Kathaperumal et al 2009;Scandurra et al 2010;Bastida and Juste 2011;Stabel et al 2012;Faisal et al 2013). Although none of the vaccines induced sterile immunity they did slow disease progression and demonstrated that development of a vaccine that induces sterile immunity is feasible (reviewed in (Rosseels and Huygen 2008).…”