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

Current vaccines for canine leishmaniosis (CanL) provide limited protection, underscoring the need for improved immunization strategies. Multi-epitope peptide vaccine delivered via nanoparticle 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 Leishmania infantum, 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, and in vitro macrophage infection assays, while safety was evaluated through clinical follow-up. Vaccination with HisDTC elicited a protective cellular response, including sustained IFN-γ production by CD4+ and CD8+ T cells, an IgG2a-skewed humoral response, and expansion of CD4+CD8α+ double-positive memory T cells. Notably, only HisDTC-vaccinated dogs exhibited a >80% reduction in in vitro macrophage 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 delivered via PLGA nanoparticles induces durable, protective immunity against L. infantum in dogs and supports its further evaluation under natural exposure conditions.

当前用于犬利什曼病（canine leishmaniosis, CanL）的疫苗保护效力有限，凸显了优化免疫防控策略的迫切需求。通过纳米颗粒系统递送的多表位肽疫苗是极具前景的替代方案，但在犬类临床研究中仍未得到充分探索。本研究报道了编号为499/ECV的双盲临床试验结果，评估了包裹于聚乳酸-羟基乙酸共聚物（poly(lactic-co-glycolic acid), PLGA）纳米颗粒中、以Toll样受体2（Toll-like receptor 2, TLR2）和Toll样受体3（Toll-like receptor 3, TLR3）配体作为佐剂的靶向婴儿利什曼原虫（Leishmania infantum）的肽疫苗HisDTC的安全性与免疫原性。本研究纳入40只健康犬，为其接种不同配方的疫苗，并开展为期12个月的跟踪监测。研究采用流式细胞术、酶联免疫吸附试验（ELISA）及体外巨噬细胞感染实验对免疫应答进行检测，同时通过临床随访评估疫苗的安全性。接种HisDTC可诱导保护性细胞免疫应答，具体表现为CD4阳性（CD4+）与CD8阳性（CD8+）T细胞持续分泌干扰素-γ（IFN-γ）、产生以IgG2a亚型为主的体液免疫应答，以及CD4+CD8α+双阳性记忆T细胞的扩增。值得注意的是，仅接种HisDTC的犬只的体外巨噬细胞感染率降低了80%以上，且其保护效应可维持至免疫后8个月。尤为关键的是，该疫苗配方具有良好的耐受性，未观察到任何不良反应。上述研究结果表明，经聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒递送的HisDTC可在犬体内诱导持久的抗婴儿利什曼原虫保护性免疫，为其在自然暴露条件下开展进一步评估提供了依据。