Abeijon Claudia, Daifalla Nada, Krautz-Peterson Greice, Pizzirani Stefano, Beamer Gillian, Frazatti-Gallina Neuza M, Raw Isaias, Campos-Neto Antonio
DetectoGen Inc. Grafton MA.
The Forsyth Institute, Cambridge MA.
Trials Vaccinol. 2016;5:1-7. doi: 10.1016/j.trivac.2015.11.001.
In areas were human visceral leishmaniasis (VL) is endemic, the domestic dog is the main parasite reservoir in the infectious cycle of . Development of prophylactic strategies to lower the parasite burden in dogs would reduce sand fly transmission thus lowering the incidence of zoonotic VL. Here we demonstrate that vaccination of dogs with a recombinant 14kDa polypeptide of nuclear transport factor 2 () mixed with adjuvant MPLA-SE resulted in the production of specific anti- IgG antibodies as well as IFN-γ release by the animals' peripheral blood mononuclear cells stimulated with the antigen. In addition, immunization with this single and small 14kDa poplypeptide resulted in protracted progression of the infection of the animals after challenging with a high dose of virulent . Five months after challenge the parasite load was lower in the bone marrow of immunized dogs compared to non-immunized animals. The antibody response to K39, a marker of active VL, at ten months after challenge was strong and significantly higher in the control dogs than in vaccinated animals. At the study termination vaccinated animals showed significantly more liver granulomas and lymphoid hyperplasia than non-vaccinated animals, which are both histological markers of resistance to infection. Together, these results indicate that the 14kDa polypeptide is an attractive protective molecule that can be easily incorporated in a leishmanial polyprotein vaccine candidate to augment/complement the overall protective efficacy of the final product.
在人类内脏利什曼病(VL)流行的地区,家犬是其感染周期中的主要寄生虫宿主。制定降低犬类寄生虫负荷的预防策略将减少白蛉传播,从而降低人畜共患性VL的发病率。在此,我们证明用核转运因子2(NTF2)的重组14kDa多肽与佐剂MPLA-SE混合对犬进行疫苗接种,会导致动物外周血单核细胞在受到抗原刺激后产生特异性抗NTF2 IgG抗体以及释放IFN-γ。此外,用这种单一的小14kDa多肽进行免疫接种后,在用高剂量强毒株攻击动物后,感染的进展较为缓慢。攻击五个月后,免疫犬骨髓中的寄生虫负荷低于未免疫动物。攻击十个月后,对活动性VL标志物K39的抗体反应在对照犬中很强,且显著高于接种疫苗的动物。在研究结束时,接种疫苗的动物肝脏肉芽肿和淋巴样增生明显多于未接种疫苗的动物,这两者都是抗感染的组织学标志物。总之,这些结果表明14kDa多肽是一种有吸引力的保护性分子,可轻松纳入利什曼原虫多蛋白候选疫苗中,以增强/补充最终产品的整体保护效力。