Immunogenicity in dogs and protection against visceral leishmaniasis induced by a 14kDa Leishmania infantum recombinant polypeptide.

Immunogenicity in dogs and protection against visceral leishmaniasis induced by a 14kDa Leishmania infantum recombinant polypeptide.
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14kDa 婴儿利什曼原虫重组多肽对狗的免疫原性和对内脏利什曼病的保护作用。

DOI:
10.1016/j.trivac.2015.11.001
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发表时间:
2016
期刊:
Trials in vaccinology
影响因子:
--
通讯作者:
Campos-Neto,Antonio
Campos-Neto,Antonio
中科院分区:
--
文献类型:
--
作者:
Abeijon,Claudia;Daifalla,Nada;Krautz-Peterson,Greice;Pizzirani,Stefano;Beamer,Gillian;Frazatti-Gallina,NeuzaM;Raw,Isaias;Campos-Neto,Antonio

文献摘要

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在人类内脏利什曼病(VL)流行的地区,家犬是婴幼儿利什曼病感染周期中的主要寄生虫宿主。制定降低犬寄生虫负担的预防策略将减少沙蝇传播,从而降低人畜共患VL的发病率。在这里,我们证明了用重组14 kDa多肽接种狗。核运输因子2 (Li-ntf2)与辅剂bpmpla - se混合后,在抗原刺激下动物外周血单个核细胞产生特异性抗Li-ntf2 igg抗体并释放IFN-γ。此外,用这种单一的14 kDa小多肽免疫可导致动物在受到高剂量毒力l攻击后感染的长期进展。infantum。攻击5个月后,与未接种的动物相比,免疫犬骨髓中的寄生虫载量较低。在攻击后10个月,对照犬对K39(活动性VL的标记物)的抗体反应很强,明显高于接种疫苗的动物。在研究结束时,接种疫苗的动物比未接种疫苗的动物表现出更多的肝脏肉芽肿和淋巴样增生,这两者都是抗感染的组织学标志。总之,这些结果表明,14 kDa多肽是一种有吸引力的保护分子,可以很容易地结合到利什曼多蛋白候选疫苗中,以增强/补充最终产品的整体保护功效。
In areas were human visceral leishmaniasis (VL) is endemic, the domestic dog is the main parasite reservoir in the infectious cycle ofLeishmania infantum. 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 14 kDa polypeptide ofL. infantumnuclear transport factor 2 (Li-ntf2) mixed with adjuvantBpMPLA-SE resulted in the production of specific anti-Li-ntf2IgG 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 14 kDa polypeptide resulted in protracted progression of the infection of the animals after challenging with a high dose of virulentL. infantum. 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 14 kDa 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.