A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis

Area of Science:

• Veterinary Immunology
• Vaccine Development
• Microbial Pathogenesis

Background:

• Mycobacterium avium subsp. paratuberculosis (Map) causes Johne's disease (JD) in livestock.
• The relA gene is crucial for Map virulence and establishing persistent infections.
• Live attenuated vaccines are being explored to combat JD.

Purpose of the Study:

• To investigate the immune response elicited by a relA deletion mutant of Map.
• To identify potential vaccine targets for Johne's disease.
• To evaluate the efficacy of a 35-kDa membrane peptide (MMP) as a vaccine candidate, alone and within a nanoparticle (NP) delivery system.

Main Methods:

• Deletion of the relA gene in Map to create a live attenuated strain.
• Analysis of the immune response, specifically cytotoxic CD8 T cells (CTL), elicited by the ΔrelA mutant.
• Ex vivo vaccination studies using the 35-kDa membrane peptide (MMP) alone and encapsulated in poly (D, L-lactide-co-glycolide) and monophosphoryl lipid A (PLGA/MPLA) nanoparticles.

Main Results:

• Deletion of relA impairs Map's ability to establish persistent infection.
• Vaccination with the ΔrelA mutant induces CTL responses targeting intracellular bacteria.
• A 35-kDa membrane peptide (MMP) was identified as a target of the recall immune response.
• Ex vivo studies showed MMP, particularly within PLGA/MPLA nanoparticles, effectively elicits CD8 CTL responses.
• Nanoparticle formulation enhanced the CTL's capacity to eliminate intracellular bacteria.

Conclusions:

• The relA gene is essential for Map virulence, and its deletion can lead to a protective immune response.
• The 35-kDa membrane peptide (MMP) is a promising target for vaccine development against Johne's disease.
• Formulating MMP within PLGA/MPLA nanoparticles enhances its potential as a subunit vaccine for Johne's disease.