EFFECTIVE IMMUNIZATION AGAINST CUTANEOUS LEISHMANIASIS WITH RECOMBINANT BACILLE CALMETTE-GUERIN EXPRESSING THE LEISHMANIA SURFACE PROTEINASE GP63
EFFECTIVE IMMUNIZATION AGAINST CUTANEOUS LEISHMANIASIS WITH RECOMBINANT BACILLE CALMETTE-GUERIN EXPRESSING THE LEISHMANIA SURFACE PROTEINASE GP63
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DOI：
10.1073/pnas.90.24.11473
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发表时间：
1993-12-15
影响因子：
11.1
通讯作者：
RUSSELL, DG
中科院分区：
文献类型：
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作者：
CONNELL, ND;MEDINAACOSTA, E;RUSSELL, DG
利什曼原虫引起的一系列疾病折磨着世界上86个国家的人口。寄生虫可以在宿主巨噬细胞的溶酶体腔室中存活，除非这些巨噬细胞被适当地激活。尽管用原始寄生虫制剂接种疫苗可以诱导保护性免疫，但在研制人类专用疫苗方面进展甚微。本研究克隆了利什曼原虫表面蛋白酶gp63的编码基因，并将其作为胞质蛋白在卡介苗株中表达。BALB/c和CBA/J小鼠分别接种单剂量重组卡介苗，攻毒感染性大利什曼原虫或墨西哥利什曼原虫。两种小鼠菌株对L. mexicana和CBA/J菌株对L. major均有显著的保护作用，而BALB/c小鼠对L. major的生长仅有延迟。重组BCG对L. mexicana无尾线虫的攻击也产生了强烈的保护反应，表明诱导的免疫反应识别了寄生虫的细胞内形式。结果表明，表达gp63的重组卡介苗可能是一种有效的疫苗，可诱导对引起美国皮肤利什曼病的利什曼原虫产生保护性细胞介导的免疫反应。
Leishmania parasites cause a spectrum of diseases that afflict the populations of 86 countries in the world. The parasites can survive within the lysosomal compartments of the host's macrophages, unless those macrophages are appropriately activated. Despite the fact that protective immunity can be induced by vaccination with crude parasite preparations, little progress has been made toward a defined vaccine for humans. In this study the gene encoding the Leishmania surface proteinase gp63 was cloned and expressed as a cytoplasmic protein in a bacille Calmette-Guerin (BCG) vaccine strain. BALB/c and CBA/J mice were inoculated with a single dose of recombinant BCG and challenged with infective Leishmania major or Leishmania mexicana promastigotes. Significant protection was observed in both mouse strains against L. mexicana and in CBA/J against L. major, whereas only a delay in L. major growth was seen in BALB/c mice. Recombinant BCG also engendered a strong protective response against challenge with amastigotes of L. mexicana, demonstrating that the induced immune response recognized the intracellular form of the parasite. The results support the view that recombinant BCG expressing gp63 may prove a useful vaccine for inducing protective cell-mediated immune responses to Leishmania species causing American cutaneous leishmaniasis.