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首页> 外文学位 >Evaluation of Plasmodium falciparum transmission blocking immunity induced by candidate vaccine antigens Pfs25 and Pfs48/45 and naturally induced immune responses in Zambian children.
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Evaluation of Plasmodium falciparum transmission blocking immunity induced by candidate vaccine antigens Pfs25 and Pfs48/45 and naturally induced immune responses in Zambian children.

机译：评价候选疫苗抗原Pfs25和Pfs48 / 45诱导的恶性疟原虫传播阻断免疫以及赞比亚儿童的自然诱导的免疫反应。

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摘要

Malaria transmission blocking immunity exerts its effect by interrupting the transfer of the malaria parasite from an infected host to a susceptible host via reducing or blocking the obligate sexual stage development in the mosquito vector. In Plasmodium falciparum malaria two key sexual stage proteins, Pfs25 and Pfs 48/45, are vaccine candidates capable of inducing potent humoral immune responses that reduce or block malaria transmission.;We evaluated vaccination of BALB/c mice and baboons using in vivo electroporation (EP) with intramuscular injection of either Pfs25 or Pfs48/45 DNA plasmids to determine whether EP could enhance the immunogenicity and functional transmission blocking effects of these two vaccines. EP enhanced the immunogenicity of the Pfs25 DNA plasmid vaccine in mice by a magnitude of two logs with comparable antibody levels being achieved with either 0.25microg of DNA with EP or 25microg of DNA without EP. Significant functional transmission blocking was demonstrated by the standard membrane feeding assay (MFA) for all three quantities of Pfs25 DNA given with EP (0.25microg, 2.5microg or 25microg). In the baboons there was a mild increase in immunogenicity of the Pfs25 DNA vaccine given with EP after a prime and one boost; however this enhancement was not seen after a prime and two boosts. EP was associated with a modest increase in transmission blocking after DNA prime, two DNA boosts and a recombinant protein boost. Pfs48-45 DNA plasmids given with or without EP in mice showed a modest improvement in antibody production and increased transmission blocking effect with EP.;To examine age-related acquisition of naturally induced immune responses to malaria asexual and sexual stage antigens, a sero-epidemiologic field study in south west Zambia was conducted over a period of one year which encompassed two peak and one trough malaria transmission seasons. One hundred forty six subjects in three age cohorts (0-5 years, 6-10 years and 11-15 years) were enrolled. There was a significant, positive age-dependent correlation of antibody levels to recombinant Pfs48/45 to assess sexual stage immune responses and to an asexual stage parasite lysate to assess erythrocytic stage immune responses. Functional transmission blocking antibody was demonstrated by MFA with a significant rise in the oldest age group. There was a high degree of concordance between the asexual and sexual antibody levels. Significant rise in antibody levels to the asexual stage antigens occurred by four years of age whereas the rise in antibody levels to the sexual stage protein occurred later at age ten years. Further studies were suggested by these observations to evaluate the importance of such natural immunity for vaccine development.
机译：疟疾传播阻断免疫通过减少或阻断蚊媒中专性性发育来中断疟原虫从感染宿主向易感宿主的转移而发挥其作用。在恶性疟原虫疟疾中，两个关键的性阶段蛋白Pfs25和Pfs 48/45是能够诱导有效的体液免疫反应的疫苗候选物，这些免疫反应可减少或阻断疟疾的传播。肌内注射Pfs25或Pfs48 / 45 DNA质粒来确定EP是否可以增强这两种疫苗的免疫原性和功能性传递阻断作用。 EP将Pfs25 DNA质粒疫苗在小鼠中的免疫原性提高了两个对数，用0.25μg的带EP的DNA或25μg的无EP的DNA达到了相当的抗体水平。通过标准膜饲喂测定法（MFA），可以对使用EP（0.25microg，2.5microg或25microg）的所有三种Pfs25 DNA进行显着的功能传递阻断。在狒狒中，初免和加强免疫后，EP接种的Pfs25 DNA疫苗的免疫原性有轻度增加。但是，经过一次加倍和两次加倍后，才看到这种增强。 EP与DNA引发，两次DNA增强和重组蛋白增强后的传导阻滞适度增加有关。给予或不给予EP的Pfs48-45 DNA质粒在小鼠中显示出适度的抗体产生改善，并增加了EP的传播阻断作用。要检查与年龄相关的自然诱导的对疟疾无性和性阶段抗原的免疫应答，请使用血清在赞比亚西南部进行了为期一年的流行病学现场研究，包括两个高峰期和一个低谷期疟疾传播季节。纳入三个年龄组（0-5岁，6-10岁和11-15岁）的146名受试者。抗体水平与重组Pfs48 / 45评估性阶段免疫反应以及无性阶段寄生虫裂解液评估红细胞阶段免疫反应之间存在显着的年龄相关性正相关。 MFA证明了功能性传递阻断抗体，并且在最老的年龄组中有明显的上升。无性和性抗体水平之间高度一致。无性阶段抗原的抗体水平显着上升发生在四岁时，而性阶段蛋白的抗体水平上升发生在十岁以后。这些观察结果提出了进一步的研究，以评估这种天然免疫对于疫苗开发的重要性。

著录项

  • 作者

    LeBlanc, Ralph E.;

  • 作者单位

    The Johns Hopkins University.;

  • 授予单位 The Johns Hopkins University.;
  • 学科 Biology Microbiology.;Health Sciences Epidemiology.;Health Sciences Public Health.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 259 p.
  • 总页数 259
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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