Nosocomial Infections Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Immunology Department, Pasteur Institute of Iran, Tehran, Iran.
PLoS One. 2018 Sep 24;13(9):e0204491. doi: 10.1371/journal.pone.0204491. eCollection 2018.
One strategy to control leishmaniasis is vaccination with potent antigens alongside suitable adjuvants. The use of toll-like receptor (TLR) agonists as adjuvants is a promising approach in Leishmania vaccine research. Leishmania (L.) tropica is among the less-investigated Leishmania species and a causative agent of cutaneous and sometimes visceral leishmaniasis with no approved vaccine against it. In the present study, we assessed the adjuvant effects of a TLR4 agonist, monophosphoryl lipid A (MPL) and a TLR7/8 agonist, R848 beside two different types of Leishmania vaccine candidates; namely, whole-cell soluble L. tropica antigen (SLA) and recombinant L. tropica stress-inducible protein-1 (LtSTI1). BALB/c mice were vaccinated three times by the antigens (SLA or LtSTI1) with MPL or R848 and then were challenged by L. tropica. Delayed-type hypersensitivity (DTH), parasite load, disease progression and cytokines (IL-10 and IFN-γ) responses were assessed. In general compared to SLA, application of LtSTI1 resulted in higher DTH, higher IFN-γ response and lower lymph node parasite load. Also compared to R848, MPL as an adjuvant resulted in higher DTH and lower lymph node parasite load. Although, no outstanding ability for SLA and R848 in evoking immune responses of BALB/c mice against L. tropica infection could be observed, our data suggest that LtSTI1 and MPL have a better potential to control L. tropica infection and could be pursued for the development of effective vaccination strategies.
一种控制利什曼病的策略是使用有效抗原与合适佐剂进行疫苗接种。使用 Toll 样受体 (TLR) 激动剂作为佐剂是利什曼病疫苗研究中的一种很有前途的方法。热带利什曼原虫(L. tropica)是研究较少的利什曼原虫物种之一,是皮肤利什曼病和有时内脏利什曼病的病原体,目前尚无针对该病原体的批准疫苗。在本研究中,我们评估了 TLR4 激动剂单磷酰脂质 A (MPL) 和 TLR7/8 激动剂 R848 与两种不同类型的利什曼病候选疫苗(即全细胞可溶性 L. tropica 抗原 (SLA) 和重组 L. tropica 应激诱导蛋白-1 (LtSTI1))联合使用的佐剂效果。BALB/c 小鼠用 SLA 或 LtSTI1 抗原免疫接种 3 次,并用 MPL 或 R848 佐剂接种,然后用 L. tropica 进行攻毒。评估迟发型超敏反应 (DTH)、寄生虫负荷、疾病进展和细胞因子(IL-10 和 IFN-γ)反应。一般来说,与 SLA 相比,应用 LtSTI1 导致更高的 DTH、更高的 IFN-γ 反应和更低的淋巴结寄生虫负荷。此外,与 R848 相比,MPL 作为佐剂可引起更高的 DTH 和更低的淋巴结寄生虫负荷。尽管没有观察到 SLA 和 R848 对 BALB/c 小鼠针对 L. tropica 感染的免疫反应有明显的作用,但我们的数据表明 LtSTI1 和 MPL 具有更好的控制 L. tropica 感染的潜力,可用于开发有效的疫苗接种策略。