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疟原虫环子孢子蛋白衍生合成多肽在 Montanide ISA 720 和 Montanide ISA 51 佐剂中的临床前疫苗研究。

Preclinical vaccine study of Plasmodium vivax circumsporozoite protein derived-synthetic polypeptides formulated in montanide ISA 720 and montanide ISA 51 adjuvants.

机构信息

Instituto de Inmunología del Valle, Universidad del Valle, Cali, Colombia.

出版信息

Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):21-7. doi: 10.4269/ajtmh.2011.10-0110.

Abstract

Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate previously assessed in animals and humans. Here, combinations of three synthetic polypeptides corresponding to amino (N), central repeat (R), and carboxyl (C) regions of the CS protein formulated in Montanide ISA 720 or Montanide ISA 51 adjuvants were assessed for immunogenicity in rodents and primates. BALB/c mice and Aotus monkeys were divided into test and control groups and were immunized three times with doses of 50 and 100 μg of vaccine or placebo. Antigen-specific antimalarial antibodies were determined by enzyme-linked immunosorbent assay, immunofluorescent antibody test, and IFN-γ responses by enzyme-linked immunosorbent spot (ELIspot). Both vaccine formulations were highly immunogenic in both species. Mice developed better antibody responses against C and R polypeptides, whereas the N polypeptide was more immunogenic in monkeys. Anti-peptide antibodies remained detectable for several months and recognized native proteins on sporozoites. Differences between Montanide ISA 720 and Montanide ISA 51 formulations were not significant.

摘要

疟原虫环子孢子蛋白(CS)是一种主要的疟疾候选疫苗,先前已在动物和人类中进行了评估。在此,用三种合成多肽组合,分别对应 CS 蛋白的氨基(N)、中心重复(R)和羧基(C)区域,用 Montanide ISA 720 或 Montanide ISA 51 佐剂配制,评估其在啮齿动物和灵长类动物中的免疫原性。BALB/c 小鼠和食蟹猴分为实验组和对照组,用 50 和 100μg 疫苗或安慰剂进行三次免疫接种。通过酶联免疫吸附试验(ELISA)、免疫荧光抗体试验(IFA)和酶联免疫斑点试验(ELIspot)测定抗原特异性抗疟抗体和 IFN-γ 反应。两种疫苗制剂在两种物种中均具有高度的免疫原性。小鼠对 C 和 R 多肽产生了更好的抗体反应,而 N 多肽在猴子中更具免疫原性。抗肽抗体在几个月内仍可检测到,并能识别孢子上的天然蛋白。Montanide ISA 720 和 Montanide ISA 51 制剂之间的差异不显著。

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