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基于 HSP70 和 HSP83 的疫苗制剂在感染杜氏利什曼原虫的 BALB/c 小鼠中的保护效力和免疫原性研究。

Studies on the protective efficacy and immunogenicity of Hsp70 and Hsp83 based vaccine formulations in Leishmania donovani infected BALB/c mice.

机构信息

Department of Zoology, Panjab University, Chandigarh 160014, India.

出版信息

Acta Trop. 2011 Jul;119(1):50-6. doi: 10.1016/j.actatropica.2011.04.007. Epub 2011 Apr 21.

Abstract

Visceral leishmaniasis, a chronic systemic infection, is the major cause of morbidity and mortality in many parts of world. The current drugs for the treatment of leishmaniasis are toxic, expensive, difficult to administer and becoming ineffective due to the emergence of drug resistance. In the absence of effective treatment, vaccination remains the only hope for control of the disease. We have evaluated the protective efficacy of two heat shock proteins (Hsp70 and Hsp83) in combination with two different adjuvants (MPLA and ALD) in Leishmania donovani infected inbred BALB/c mice. The proteins were isolated by SDS-PAGE and the mice were immunized subcutaneously with Hsp70+Hsp83, Hsp70+Hsp83+ALD and Hsp70+Hsp83+MPLA. These were challenged with 10(7) promastigotes of L. donovani. The animals were sacrificed on 30, 60 and 90 days post challenge for the assessment of parasite load and generation of cellular and humoral immune responses. The vaccines induced a strong protective response against experimental visceral leishmaniasis as shown by reduced parasite load in liver of all immunized groups as compared to the infected controls. The vaccines also led to the augmentation of DTH responses, increased levels of IgG2a, IFN-γ and IL-2. Both the adjuvants raised significantly the level of protection imparted by the proteins but MPLA was more effective in comparison to ALD.

摘要

内脏利什曼病是一种慢性全身性感染,是世界许多地区发病率和死亡率的主要原因。目前用于治疗利什曼病的药物具有毒性、昂贵、难以管理且由于耐药性的出现而变得无效。在缺乏有效治疗的情况下,疫苗接种仍然是控制该病的唯一希望。我们评估了两种热休克蛋白(Hsp70 和 Hsp83)与两种不同佐剂(MPLA 和 ALD)联合用于感染同基因 BALB/c 小鼠的利什曼原虫的保护效力。通过 SDS-PAGE 分离蛋白质,并用 Hsp70+Hsp83、Hsp70+Hsp83+ALD 和 Hsp70+Hsp83+MPLA 对小鼠进行皮下免疫。用 10(7)个利什曼原虫前鞭毛体对这些动物进行攻击。在挑战后 30、60 和 90 天处死动物,以评估寄生虫负荷和细胞及体液免疫反应的产生。疫苗诱导了针对实验性内脏利什曼病的强烈保护反应,与感染对照组相比,所有免疫组的肝脏寄生虫负荷均降低。疫苗还导致 DTH 反应增强,IgG2a、IFN-γ 和 IL-2 水平升高。两种佐剂都显著提高了蛋白质赋予的保护水平,但与 ALD 相比,MPLA 更有效。

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