A comparative evaluation of different DNA vaccine candidates against experimental murine leishmaniasis due to L-major

A comparative evaluation of different DNA vaccine candidates against experimental murine leishmaniasis due to L-major
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DOI:
10.1016/j.vaccine.2003.10.046
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发表时间:
2004-04-16
期刊:
影响因子:
5.5
通讯作者:
Dellagi, K
Dellagi, K
中科院分区:
医学3区
文献类型:
--
作者:
Ahmed, SB;Bahloul, C;Dellagi, K

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在过去的几年里,一些关于小鼠皮肤实验性利什曼病的DNA疫苗的报道出现了有希望的,但有时不一致的结果。本研究的目的是比较,在相似的条件下,在高度易感的BALB/c小鼠的DNA疫苗候选人编码的各种主要利什曼原虫抗原的保护作用。候选DNA疫苗编码以下抗原:LACK、PSA 2、Gp 63、LeIF和两种新鉴定的p20和核糖体样蛋白,以及LACK抗原的不同截短部分。最有希望的基因是LACK,当它作为p24截短形式使用时,它更具保护性。此外,质粒骨架中免疫刺激序列(ISS)的串联重复序列的存在在所观察到的由编码LACKp 24的DNA疫苗诱导的保护作用中发挥了重要的佐剂作用。然而,这两种DNA疫苗候选物都不能在用高度毒力的L.主要菌株。仍需要进一步改进DNA疫苗接种方法以设计针对利什曼病的完全保护性疫苗。目前研究的三个方向是:使用抗原混合物的DNA疫苗; Prime/Boost方法;以及将免疫调节剂与候选抗原结合。(C)2004爱思唯尔有限公司保留所有权利。
Over the past few years, several reports of DNA vaccines against murine cutaneous experimental leishmaniasis came out with promising but sometimes discordant results. The present studies were designed to compare, under similar conditions, the protective effects in the highly susceptible BALB/c mice of DNA vaccine candidates encoding to various Leishmania major antigens. The candidate DNA vaccines encode to the following antigens: LACK, PSA2, Gp63, LeIF and two newly identified p20 and Ribosomal like protein, in addition to different truncated portions of the LACK antigen. The most promising gene was LACK and it is more protective when it is used as a p24 truncated form. Furthermore, the presence of a tandem repeats of immumostimulating sequences (ISS) in the plasmid backbone played an important adjuvant effect in the observed protective effect induced by the DNA vaccine encoding to the LACKp24. Nevertheless, neither of the DNA vaccine candidates was able to mount a full protection in BALB/c mice challenged with a highly virulent L. major strain. Further improvements of the DNA vaccination approach are still needed to design a fully protective vaccine against leishmaniasis. Three directions of investigations are currently explored: DNA vaccines using a cocktail of antigens; Prime/Boost approach; and association of immune modulators with the candidate antigens. (C) 2004 Elsevier Ltd. All rights reserved.