A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis

Authors

Gaber S. Abdellrazeq, Washington State University, Pullman & Alexandria University
Mahmoud M. Elnaggar, Washington State University, Pullman &Alexandria University
J. P. Bannantine, USDA-ARS, National Animal Disease CenterFollow
David A. Schneider, Washington State University, Pullman & USDA, ARS, Animal Disease Research Unit
Cleverson D. Souza, Washington State University, Pullman
Julianne Hwang, Washington State University, Pullman
Asmaa H.A. Mahmoud, Washington State University, Pullman & Ministry of Agriculture, Egypt
Victoria Hulubei, Washington State University, PullmanFollow
Lindsay M. Fry, Washington State University, Pullman & USDA, ARS, Animal Disease Research Unit
Kun-Taek Park, Inje University
William C. Davis, Washington State University, PullmanFollow

Date of this Version

2019

Citation

Vaccine 37 (2019) 2783–2790

https://doi.org/10.1016/j.vaccine.2019.04.040

Comments

U.S. government works are not subject to copyright.

Abstract

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 (DrelA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by DrelA 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 intra- cellular 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.