A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis

Authors: ABDELLRAZEQ, GABER - Washington State University; ELNAGGAR, MAHMOUD - Washington State University; Bannantine, John; SCHNEIDER, DAVID - US Department Of Agriculture (USDA); SOUZA, CLEVERSON - Washington State University; HWANG, JULIANNE - Washington State University; MAHMOUD, ASMAA - Washington State University; HULUBEI, VICTORIA - Washington State University; FRY, LINDSAY - US Department Of Agriculture (USDA); PARK, KUNTAEK - Inje University; DAVIS, WILLIAM - Washington State University

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/2019
Publication Date: 4/16/2019
Citation: Abdellrazeq, G.S., Elnaggar, M.M., Bannantine, J.P., Schneider, D.A., Souza, C.D., Hwang, J., Mahmoud, A.H., Hulubei, V., Fry, L.M., Park, K., Davis, W.C. 2019. A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis. Vaccine. 37(21):2783-2790. https://doi.org/10.1016/j.vaccine.2019.04.040.
DOI: https://doi.org/10.1016/j.vaccine.2019.04.040

Interpretive Summary: The goal of this study was to develop and test a peptide vaccine in terms of its ability to arm a type of immune cell (cytotoxic T cells) to kill Mycobacterium avium subspecies paratuberculosis, the bacteria that causes Johne's disease. The peptide selection was a major membrane protein that has previously shown promise as a vaccine candidate. The peptide was tested alone and formulated as a nanoparticle. It was discovered that the nanoparticle formulation of this membrane protein was the best at priming the T cells to kill the bacteria. This work is of interest to animal producers, veterinarians and researchers.

Technical 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 lowers the ability of Map to establish a persistent infection. Analysis of the basis for this observation revealed infection with a relA deletion mutant ('relA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by 'relA 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. The findings show incorporating MMP into a NP vector enhances the ability of CD8 CTL to kill intracellular bacteria ex vivo, which is similar to that observed with the relA mutant. These findings open up the possibility for development of both a subunit nanopartical vaccine (MMP) and a live attenuated vaccine ('relA) against Johne’s disease.