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利什曼原虫重组主要表面糖蛋白(rgp63)脂质体重构物在BALB/c小鼠中的免疫应答及保护试验

Immune response and protection assay of recombinant major surface glycoprotein of Leishmania (rgp63) reconstituted with liposomes in BALB/c mice.

作者信息

Jaafari Mahmoud R, Ghafarian Attieh, Farrokh-Gisour Ahsan, Samiei Afshin, Kheiri Masoumeh Tavassoti, Mahboudi Fereidoun, Barkhordari Farzaneh, Khamesipour Ali, McMaster W Robert

机构信息

School of Pharmacy, Biotechnology Research Center, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.

出版信息

Vaccine. 2006 Jul 17;24(29-30):5708-17. doi: 10.1016/j.vaccine.2006.04.062. Epub 2006 May 11.

Abstract

In this study the ability of recombinant gp63 entrapped in liposomes to induce immune response and protection against L. major infection in susceptible BALB/c mice was studied. Liposomes containing rgp63 (Lip-rgp63) were prepared from egg lecithin and cholesterol using detergent solubilization method. Immunization of BALB/c mice with rgp63 alone conferred a partial protection while entrapment of rgp63 in liposomes significantly increased the rate of protection (P<0.05). The parasite burden of spleen in mice challenged with L. major was significantly (p<0.001) lower in group of mice immunized with rgp63 alone or Lip-rgp63, however, the least parasite burden was seen in Lip-rgp63 group. Both rgp63 alone and Lip-rgp63 elicited significant delayed-type hypersensitivity (DTH) response compared to controls (p<0.01), however, the DTH response of PBS-rgp63 was less than the Lip-rgp63. Titration of anti-Leishmania IgG isotypes (IgG2a/IgG1) showed a preferential Th1 type of immune response only in mice immunized with Lip-rgp63. The results indicate that liposomes might be used as a suitable immunoadjuvant for development of Leishmania vaccine.

摘要

在本研究中,研究了包裹在脂质体中的重组gp63在易感BALB/c小鼠中诱导免疫反应及预防硕大利什曼原虫感染的能力。采用去污剂增溶法,由卵磷脂和胆固醇制备了含rgp63的脂质体(Lip-rgp63)。单独用rgp63免疫BALB/c小鼠可提供部分保护,而将rgp63包裹在脂质体中可显著提高保护率(P<0.05)。用硕大利什曼原虫攻击的小鼠中,单独用rgp63或Lip-rgp63免疫的小鼠脾脏中的寄生虫负荷显著降低(p<0.001),然而,Lip-rgp63组的寄生虫负荷最低。与对照组相比,单独的rgp63和Lip-rgp63均引发了显著的迟发型超敏反应(DTH)(p<0.01),然而,PBS-rgp63的DTH反应小于Lip-rgp63。抗利什曼原虫IgG同种型(IgG2a/IgG1)的滴定显示,仅在用Lip-rgp63免疫的小鼠中出现了优先的Th1型免疫反应。结果表明,脂质体可能用作开发利什曼原虫疫苗的合适免疫佐剂。

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