Abstract：
Leishmaniasis is the 3rd most challenging vector-borne disease after malaria and lymphatic filariasis. Currently, no vaccine candidate is approved or marketed against leishmaniasis due to difficulties in eliciting broad immune responses when using sub-unit vaccines. The aim of this work was the design of a particulate sub-unit vaccine for vaccination against leishmaniasis. The poly (D,L-lactide) nanoparticles (PLA-NPs) were developed in order to efficiently adsorb a recombinant L. major histone H2B (L. major H2B) and to boost its immunogenicity. Firstly, a study was focused on the production of well-formed nanoparticles by the nanoprecipitation method without using a surfactant and on the antigen adsorption process under mild conditions. The set-up preparation method permitted to obtain H2B-adsorbed nanoparticles H2B/PLA (adsorption capacity of about 2.8% (w/w)) with a narrow size distribution (287 nm) and a positive zeta potential (30.9 mV). Secondly, an in vitro release assay performed at 37 °C, pH 7.4, showed a continuous release of the adsorbed H2B for almost 21 days (30%) from day 7. The immune response of H2B/PLA was investigated and compared to H2B + CpG7909 as a standard adjuvant. The humoral response intensity (IgG) was substantially similar between both formulations. Interestingly, when challenged with the standard parasite strain (GLC94) isolated from a human lesion of cutaneous leishmaniasis, mice showed a significant reduction in footpad swelling compared to unvaccinated ones, and no deaths occurred until week 17th. Taken together, these results demonstrate that PLA-NPs represent a stable, cost-effective delivery system adjuvant for use in vaccination against leishmaniasis.
摘要：
利什曼病是仅次于疟疾和淋巴丝虫病的第三大最具挑战性的媒介传播疾病。目前,由于使用亚单位疫苗时难以引发广泛的免疫反应,因此没有针对利什曼病的候选疫苗获得批准或上市.这项工作的目的是设计一种用于接种利什曼病的微粒亚单位疫苗。聚(D,为了有效吸附重组L.主要组蛋白H2B（L.主要H2B)并增强其免疫原性。首先,一项研究的重点是在不使用表面活性剂的情况下通过纳米沉淀方法生产形成良好的纳米颗粒，以及在温和条件下的抗原吸附过程。该设置的制备方法允许获得具有窄尺寸分布(287nm)和正ζ电位(30.9mV)的H2B吸附的纳米颗粒H2B/PLA(吸附容量为约2.8%(w/w))。其次,在37°C下进行的体外释放测定，从第7天开始,pH7.4显示吸附的H2B连续释放近21天(30%)。研究H2B/PLA的免疫应答并与作为标准佐剂的H2B+CpG7909进行比较。两种制剂之间的体液应答强度(IgG)基本上相似。有趣的是,当受到从人类皮肤利什曼病病变中分离出的标准寄生虫菌株（GLC94）的攻击时，与未接种疫苗的小鼠相比，足垫肿胀显着减少，直到第17周都没有死亡。一起来看,这些结果表明，PLA-NP代表稳定的，用于接种利什曼病疫苗的经济有效的递送系统佐剂。
