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

Area of Science:

• Veterinary immunology
• Ruminant infectious diseases
• Vaccine development

Background:

• Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) causes Johne's disease in ruminants, leading to significant economic losses.
• Existing control strategies for Johne's disease are limited, necessitating the development of effective vaccines.
• Live-attenuated vaccines are being explored as a promising approach for controlling intracellular pathogens.

Purpose of the Study:

• To evaluate the efficacy of two novel live-attenuated vaccine candidates, pgsH and pgsN, against M. paratuberculosis challenge in a goat model.
• To compare the performance of these live-attenuated vaccines with an inactivated vaccine and unvaccinated controls.

Main Methods:

• Development of two live-attenuated vaccine candidates (pgsH and pgsN) with mutations in sigH and lipN genes.
• Experimental infection of goats with wild-type M. paratuberculosis following vaccination.
• Assessment of vaccine efficacy through monitoring histopathological lesions, tissue colonization, fecal shedding, and cell-mediated immune responses.

Main Results:

• Both pgsH and pgsN vaccines conferred significant immunity, reducing lesions and tissue colonization compared to unvaccinated and inactivated vaccine groups.
• The pgsN vaccine candidate demonstrated the ability to eliminate fecal shedding in challenged goats, a critical factor for disease control.
• Goats vaccinated with pgsN exhibited strong initial cell-mediated immune responses not observed in other groups.

Conclusions:

• Live-attenuated vaccines, particularly the pgsN construct, show significant potential for controlling Johne's disease in ruminants.
• The pgsN vaccine's ability to reduce shedding and elicit cell-mediated immunity makes it a highly desirable candidate.
• Further investigation in cattle is warranted to establish this vaccine's role in broader Johne's disease control programs.