%X Development of a protective vaccine against Leishmania depends on antigen formulation and adjuvants that induce specific immunity and long-lasting immune responses. We previously demonstrated that BALB/c mice intranasally vaccinated with a plasmid DNA encoding the p36/LACK leishmanial antigen (LACK-DNA) develop a protective immunity for up to 3 months after vaccination, which was linked with the systemic expression of vaccine mRNA in peripheral organs. In this study, LACK-DNA vaccine was associated with biocompatible chitosan microparticles cross-linked with glyceraldehyde (CMC) to boost the long-lasting immunity against the late Leishmania infantum challenge. Infection at 7 days, 3 or 6 months after vaccination resulted in significantly lower parasite loads when compared with non-vaccinated controls. Besides, LACK-DNA-chitosan vaccinated mice showed long-time protection observed after the late time point challenge. The achieved protection was correlated with an enhanced spleen cell responsiveness to parasite antigens, marked by increased proliferation and IFN-γ as well as decreased IL-10 production. Moreover, we found diminished systemic levels of TNF-α that was compatible with the better health condition observed in LACK-DNA/CMC vaccinated-infected mice. Together, our data indicate the feasibility of chitosan microparticles as a delivery system tool to extend the protective immunity conferred by LACK-DNA vaccine, which may be explored in vaccine formulations against Leishmania parasite infections. %O This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. %J Microbes and Infection %A Daniel Claudio Oliveira Gomes %A Beatriz Lilian da Silva Costa Souza %A Rodrigo Porto Schwedersky %A Luciana Polaco Covre %A Herbert Leonel de Matos Guedes %A Ulisses Gazos Lopes %A Maria Inês Ré %A Bartira Rossi-Bergmann %L discovery10164593 %I Elsevier %V 24 %K Visceral leishmaniasis, Leishmania infantum, Intranasal delivery, DNA vaccineLACK %T Intranasal immunization with chitosan microparticles enhances LACK-DNA vaccine protection and induces specific long-lasting immunity against visceral leishmaniasis %N 2 %C France %D 2022