Evaluation of the safety and immunogenicity of a peptide vaccine against canine leishmaniosis: a double-blind, multicenter, controlled clinical trial in dogs.

Abstract

Current vaccines for canine leishmaniosis (CanL) provide limited protection, underscoring the need for improved immunization strategies. Multi-epitope peptide vaccine deliverednanoparticle systems represents a promising alternative but remains underexplored in canine clinical trials. Here, we report the results of a double-blind clinical trial (499/ECV) evaluating the safety and immunogenicity of HisDTC, a peptide vaccine targeting, encapsulated in poly(lactic-co-glycolic acid) PLGA nanoparticles and adjuvanted with Toll-like receptor 2 (TLR2) and TLR3 ligands. Forty healthy dogs were immunized with different vaccine formulations and monitored over 12 months. Immune responses were assessed by flow cytometry, ELISA, andmacrophage infection assays, while safety was evaluated through clinical follow-up. Vaccination with HisDTC elicited a protective cellular response, including sustained IFN-γ production by CD4and CD8T cells, an IgG2a-skewed humoral response, and expansion of CD4CD8αdouble-positive memory T cells. Notably, only HisDTC-vaccinated dogs exhibited a >80% reduction inmacrophage infection, with protective effects persisting for up to 8 months post-immunization. Importantly, the formulation was well tolerated, with no adverse effects reported. These findings demonstrate that HisDTC deliveredPLGA nanoparticles induces durable, protective immunity againstin dogs and supports its further evaluation under natural exposure conditions.