A Canine-Directed Chimeric Multi-Epitope Vaccine Induced Protective Immune Responses in BALB/c Mice Infected with Leishmania infantum

Abstract

<jats:p>Leishmaniases are complex vector-borne diseases caused by intracellular parasites of the genus Leishmania. The visceral form of the disease affects both humans and canids in tropical, subtropical, and Mediterranean regions. One health approach has suggested that controlling zoonotic visceral leishmaniasis (ZVL) could have an impact on the reduction of the human incidence of visceral leishmaniasis (VL). Despite the fact that a preventive vaccination could help with leishmaniasis elimination, effective vaccines that are able to elicit protective immune responses are currently lacking. In the present study, we designed a chimeric multi-epitope protein composed of multiple CD8+ and CD4+ T cell epitopes which were obtained from six highly immunogenic proteins previously identified by an immunoproteomics approach, and the N-termini of the heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis served as an adjuvant. A preclinical evaluation of the candidate vaccine in BALB/c mice showed that when it was given along with the adjuvant Addavax it was able to induce strong immune responses. Cellular responses were dominated by the presence of central and effector multifunctional CD4+ and CD8+ T memory cells. Importantly, the vaccination reduced the parasite burden in both short-term and long-term vaccinated mice challenged with Leishmania infantum. Protection was characterized by the continuing presence of IFN-γ+TNFα+-producing CD8+ and CD4+ T cells and increased NO levels. The depletion of CD8+ T cells in short-term vaccinated mice conferred a significant loss of protection in both target organs of the parasite, indicating a significant involvement of this population in the protection against L. infantum challenge. Thus, the overall data could be considered to be a proof-of-concept that the design of efficacious T cell vaccines with the help of reverse vaccinology approaches is possible.</jats:p>

Designing of a Novel Fusion Protein Vaccine Candidate Against Human Visceral Leishmaniasis (VL) Using Immunoinformatics and Structural Approaches

“…To this end, identifying reliable B cell epitopes from protein sequence can be helpful (Irvine and Read 2020 ). Because visceral leishmaniasis (VL) is an intracellular parasite, cytotoxic T-cell lymphocyte (CTL) can play an important role in regulating a protective response to it; therefore, identification of CTL epitopes can help to develop cell-mediated immunity (Stager and Rafati 2012 ; Agallou, Margaroni et al 2020 ). Bioinformatics software’s are able to provide useful information about the characteristics of the candidate vaccine as well as the improvement of its properties (Poland and Oberg 2010 ; María, Arturo et al 2017 ).…”

Applied Proteomics in ‘One Health’

“…In total, 42 protein spots were found to differentially react with IgG from asymptomatic hosts and could be used as candidate antigens for vaccine development. Subsequently, a chimeric multi-epitope protein composed of multiple CD8 + and CD4 + T cell epitopes was designed in order to develop a novel vaccine against the protozoon [ 213 ].…”

A T-Cell Epitope-Based Multi-Epitope Vaccine Designed Using Human HLA Specific T Cell Epitopes Induces a Near-Sterile Immunity against Experimental Visceral Leishmaniasis in Hamsters

“…Regarding novel vaccine candidates with a tailored response, immunoinformatic-predicted T cell-specific epitopes can be used to generate newer candidates [31,32]. Advancement in prediction models of linear and conformational epitopes has significantly boosted vaccine research in the last decades with the emergence of many epitope-based vaccine candidates for Leishmania donovani, L. major, and, L. infantum [33][34][35][36][37][38][39], and also for other diseases [40][41][42][43][44]. Keeping in mind the immune-correlates of protection in L. donovani infection, we have used the strategy of designing multiple vaccine candidates either by the addition of various T cell epitopes in a single multi-epitope candidate or with the use of multiple IFN-γ inducing epitopes to generate different multi-epitope constructs.…”