Hurtado Morillas, ClaraMartínez Rodrigo, AbelOrden Gutiérrez, José AntonioDe Urbina Fuentes, LauraMas Zubiri, AliciaDomínguez Bernal, Gustavo Ramón2024-04-222024-04-222024-02-13Hurtado-Morillas, C.; Martínez-Rodrigo, A.; Orden, J.A.; de Urbina-Fuentes, L.; Mas, A.; Domínguez-Bernal, G. Enhancing Control of Leishmania infantum Infection: A Multi-Epitope Nanovaccine for Durable T-Cell Immunity. Animals 2024, 14, 605. https://doi.org/10.3390/ ani140406052076-261510.3390/ ani14040605https://hdl.handle.net/20.500.14352/103346Author Contributions: Conceptualization, A.M.-R., A.M. and G.D.-B.; Formal analysis, C.H.-M., A.M.-R. and G.D.-B.; Funding acquisition, G.D.-B.; Investigation, C.H.-M., A.M. and G.D.-B.; Methodology, C.H.-M., A.M.-R. and L.d.U.-F.; Project administration, G.D.-B.; Supervision, A.M.-R., A.M. and G.D.-B.; Writing—original draft, C.H.-M. and A.M.-R.; Writing—review and editing, A.M.-R., J.A.O., A.M. and G.D.-B. All authors have read and agreed to the published version of the manuscript.Canine leishmaniosis (CanL) is a growing health problem for which vaccination is a crucial tool for the control of disease. The successful development of an effective vaccine against this disease relies on eliciting a robust and enduring T-cell immune response involving the activation of CD4+ Th1 and CD8+ T-cells. This study aimed to evaluate the immunogenicity and prophylactic efficacy of a novel nanovaccine comprising a multi-epitope peptide, known as HisDTC, encapsulated in PLGA nanoparticles against Leishmania infantum infection in the murine model. The encapsulation strategy was designed to enhance antigen loading and sustain release, ensuring prolonged exposure to the immune system. Our results showed that mice immunized with PLGA-encapsulated HisDTC exhibited a significant reduction in the parasite load in the liver and spleen over both short and long-term duration. This reduction was associated with a cellular immune profile marked by elevated levels of pro-inflammatory cytokines, such as IFN-γ, and the generation of memory T cells. In conclusion, the current study establishes that PLGA-encapsulated HisDTC can promote effective and long-lasting T-cell responses against L. infantum in the murine model. These findings underscore the potential utility of multi-epitope vaccines, in conjunction with appropriate delivery systems, as an alternative strategy for CanL control.Simple Summary: Canine leishmaniosis is a potentially fatal disease in dogs caused by the Leishmania parasite. Vaccination seems to be the safest, most cost-effective, and long-lasting control strategy. Currently, there is still no vaccine that totally guarantees complete protection against Leishmania infection. Here, we designed and evaluated the effectiveness of a nanovaccine against Leishmania infantum infection in the murine model. This vaccine strategy, consisting of the HisDTC peptide encapsulated in polymeric nanoparticles, induced in vaccinated groups a lower parasite load in comparison to the control groups, which was correlated with the induction of a cellular immune response profile against Leishmania infantum measured throughout different cytokines, antibodies titers, and memory T cells. These results provide evidence that the HisDTC peptide encapsulated in polymeric nanoparticles is a potential vaccine strategy against canine leishmaniosis.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.3390/ ani14040605open access636.09Canine leishmaniosisPLGA nanoparticlesMulti-epitope peptideNanovaccineLetiFend®Leishmania infantumVeterinaria3109 Ciencias Veterinarias