© 2020 Elsevier B.V. Re-emergence and geographic expansion of leishmaniasis is accelerating efforts to develop a safe and effective Leshmania vaccine. Vaccines using Leishmania recombinant antigens, such as LiHyp1, which is mostly present in the amastigote parasite form, are being developed as a next generation to crude killed parasite-based vaccines. The main objective of this work was to develop a LiHyp1-based vaccine and determine if it can induce protective immunity in BALB/c mice when administered using a dissolvable microneedle (DMN) patch by the skin route. The LiHyp1 antigen was incorporated into cationic liposomes (CL), with or without the TLR9 agonist, CpG. The LiHyp1-liposomal vaccines were characterized with respect to size, protein encapsulation rates and retention of their physical characteristics after incorporation into the DMN patch. DMN mechanical strength and skin penetration ability were tested. A vaccine composed of LiHyp1, CpG and liposomes and subcutaneously injected or a vaccine containing antigen and CpG in DMN patches, without liposomes, induced high antibody responses and significant levels of protection against L. donovani parasite infection. This study progresses the development of an efficacious leishmania vaccine by detailing promising vaccine formulations and skin delivery technologies and it addresses protective efficacy of a liposome-based dissolvable microneedle patch vaccine system.