A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis.
Recent efforts to develop a live attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of Johne's disease (JD), revealed relA is important in Map virulence. Deletion of the relA gene impairs the ability of Map to establish a persistent infection. Analysis of the basis for this observation revealed infection with a relA deletion mutant (ΔrelA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by ΔrelA vaccination showed a 35 kDa membrane peptide (MMP) is one of the targets of the immune response, suggesting it might be possible to develop a peptide-based vaccine based on MMP. To explore this possibility, ex vivo vaccination studies were conducted with MMP alone and incorporated into a nanoparticle (NP) vector comprised of poly (D, L-lactide-co-glycolide) and monophosphoryl lipid A (PLGA/MPLA). As reported, ex vivo vaccination studies showed CD8 CTL were elicited with classic and monocyte derived dendritic cells (cDC and MoDC) pulsed with MMP alone and incorporated into a PGLA/MPLA vector. Incorporation of MMP into a NP vector enhanced the ability of CD8 CTL to kill intracellular bacteria. The findings indicate incorporation of MMP into a PGLA/MPLA nanoparticle vector is one of the possible ways to develop a MMP based vaccine for Johne's disease.
['Abdellrazeq|Gaber S|GS|', 'Elnaggar|Mahmoud M|MM|', 'Bannantine|John P|JP|', 'Schneider|David A|DA|', 'Souza|Cleverson D|CD|', 'Hwang|Julianne|J|', 'Mahmoud|Asmaa H A|AHA|', 'Hulubei|Victoria|V|', 'Fry|Lindsay M|LM|', 'Park|Kun-Taek|KT|', 'Davis|William C|WC|']
D000818:Animals D001426:Bacterial Proteins D001428:Bacterial Vaccines D018414:CD8-Positive T-Lymphocytes D002417:Cattle D005434:Flow Cytometry D016927:Mycobacterium avium subsp. paratuberculosis D053758:Nanoparticles D010455:Peptides D000077182:Polylactic Acid-Polyglycolic Acid Copolymer D013602:T-Lymphocytes, Cytotoxic
Mycobacterium avium subspecies paratuberculosis Monocyte derived dendritic cells Bovine Cytotoxic T cells Flow cytometry Intracellular killing Propidium monoazide Zoonotic pathogen