评估一种灭活候选疫苗与不同佐剂联合使用对小鼠内脏利什曼病的免疫预防潜力。

Evaluation of the immunoprophylactic potential of a killed vaccine candidate in combination with different adjuvants against murine visceral leishmaniasis.

作者信息

Thakur Ankita, Kaur Harpreet, Kaur Sukhbir

机构信息

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

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

出版信息

Parasitol Int. 2015 Feb;64(1):70-8. doi: 10.1016/j.parint.2014.10.003. Epub 2014 Oct 12.

Abstract

Despite a large number of field trials, till date no prophylactic antileishmanial vaccine exists for human use. Killed antigen formulations offer the advantage of being safe but they have limited immunogenicity. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to the lack of an appropriate adjuvant. Addition of adjuvants to vaccines boosts and directs the immunogenicity of antigens. So, the present study was done to evaluate the effectiveness of four adjuvants i.e. alum, saponin, cationic liposomes and monophosphoryl lipid-A in combination with Autoclaved Leishmania donovani (ALD) antigen against murine visceral leishmaniasis (VL). BALB/c mice were immunized thrice with respective vaccine formulation. Two weeks after last booster, challenge infection was given. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post infection/challenge days. A considerable protective efficacy was shown by all vaccine formulations. It was evident from significant reduction in parasite load, profound delayed type hypersensitivity responses (DTH), increased IgG2a titres and high levels of Th1 cytokines (IFN-γ, IL-12) as compared to the infected controls. However, level of protection varied with the type of adjuvant used. Maximum protection was achieved with the use of liposome encapsulated ALD antigen and it was closely followed by group immunized with ALD+MPL-A. Significant results were also obtained with ALD+saponin, ALD+alum and ALD antigen (alone) but the protective efficacy was reduced as compared to other immunized groups. The present study reveals greater efficacy of two vaccine formulations i.e. ALD+liposome and ALD+MPL-A against murine VL.

摘要

尽管进行了大量的现场试验,但迄今为止,仍没有可供人类使用的预防性抗利什曼原虫疫苗。灭活抗原制剂具有安全的优点,但免疫原性有限。最近的研究表明,由于缺乏合适的佐剂,开发有效的利什曼原虫疫苗的努力受到了限制。向疫苗中添加佐剂可增强并引导抗原的免疫原性。因此,本研究旨在评估四种佐剂,即明矾、皂苷、阳离子脂质体和单磷酰脂质A与经高压灭菌的杜氏利什曼原虫(ALD)抗原联合使用对小鼠内脏利什曼病(VL)的有效性。用相应的疫苗制剂对BALB/c小鼠进行三次免疫。最后一次加强免疫两周后,进行攻击感染。在最后一次免疫后15天以及感染/攻击后30、60和90天处死小鼠。所有疫苗制剂均显示出相当的保护效力。与感染对照组相比,寄生虫载量显著降低、明显的迟发型超敏反应(DTH)、IgG2a滴度增加以及Th1细胞因子(IFN-γ、IL-12)水平升高,这表明了保护效力。然而,保护水平因所用佐剂的类型而异。使用脂质体包裹的ALD抗原可实现最大程度的保护,紧随其后的是用ALD+MPL-A免疫的组。ALD+皂苷、ALD+明矾和ALD抗原(单独使用)也取得了显著结果,但与其他免疫组相比,保护效力有所降低。本研究揭示了两种疫苗制剂,即ALD+脂质体和ALD+MPL-A对小鼠VL具有更高的效力。

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