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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates
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A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates

机译:由蛋白质-肽结合物组成的双组分恶性疟原虫研究疫苗

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摘要

There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia, the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes with sexual multiplication. The most common and serious type of malaria is caused by Plasmodium falciparum. The circumsporozoite protein (CSP), a major surface antigen of sporozoites, is a protective antigen. A unique feature of P. falciparum CSP is its large central domain composed of over 30 tetrapeptide repeats of Asn-Ala-Asn-Pro (NANP). Several NANP peptide-protein conjugates were tested clinically but elicited a low level of CSP antibodies for a short duration. To provide a CSP-based candidate vaccine, we investigated recombinant CSP and NANP conjugates of various peptide lengths, with different N-terminal amino acids, bound at different ratios to various carrier proteins. Injected into mice, CSP alone and CSP or NANP conjugates induced antibodies with booster responses and were positive by the sporozoite imunofluorescent assay. The use of the mosquito stage P. falciparum ookinete surface protein, Pfs25, cross-linked onto itself as a carrier for NANP, induced in mice high levels of uniquely long-lasting antibodies to both vaccine components with secondary biological activities, that will provide immunity to liver infection by sporozoites and block transmission by mosquitoes.
机译:尚无针对疟疾的许可疫苗,疟疾是一种主要影响儿童的严重人类疾病,年死亡率约为一百万。疟原虫是引起疟疾的寄生虫,有两个强制宿主:哺乳动物或鸟类,它们在其中无性繁殖,以及蚊子有性繁殖。疟疾最常见和最严重的类型是由恶性疟原虫引起的。子孢子的主要表面抗原环子孢子蛋白(CSP)是一种保护性抗原。恶性疟原虫CSP的独特功能是其大型中央结构域,由Asn-Ala-Asn-Pro(NANP)的30多个四肽重复序列组成。临床测试了几种NANP肽-蛋白质偶联物,但在短时间内引起了低水平的CSP抗体。为了提供基于CSP的候选疫苗,我们研究了具有不同N末端氨基酸,以不同比例结合到各种载体蛋白上的各种肽长度的重组CSP和NANP缀合物。单独注射CSP和CSP或NANP偶联物注射入小鼠后,可产生具有增强反应的抗体,并且通过子孢子免疫荧光试验呈阳性。蚊子阶段恶性疟原虫表面活性蛋白Pfs25自身交联后作为NANP的载体,在小鼠中诱导了高水平的两种疫苗成分的独特长效抗体的二级免疫活性,从而提供免疫力子孢子对肝脏的感染,并阻止蚊子传播。

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  • 作者单位

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Department of Pathology, Langone Medical Center, New York University School of Medicine, NY 10016;

    Department of Pathology, Langone Medical Center, New York University School of Medicine, NY 10016;

    Department of Pathology, Langone Medical Center, New York University School of Medicine, NY 10016;

    Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852;

    Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

    Program on Developmental and Molecular Immunity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    malaria; circumsporozoite protein; Asn-Ala-Asn-Pro; plasmodium falciparum ookinete surface protein 25;

    机译:疟疾;环子孢子蛋白;Asn-Ala-Asn-Pro;恶性疟原虫钩虫表面蛋白25;

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