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首页> 外文期刊>Infection and immunity >Immunogenicity of a Prime-Boost Vaccine Containing the Circumsporozoite Proteins of Plasmodium vivax in Rodents
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Immunogenicity of a Prime-Boost Vaccine Containing the Circumsporozoite Proteins of Plasmodium vivax in Rodents

机译：含间日疟原虫环子孢子蛋白的初免-加强型疫苗的免疫原性。

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Plasmodium vivax is the most widespread and the second most prevalent malaria-causing species in the world. Current measures used to control the transmission of this disease would benefit from the development of an efficacious vaccine. In the case of the deadly parasite P. falciparum, the recombinant RTS,S vaccine containing the circumsporozoite antigen (CSP) consistently protects 30 to 50% of human volunteers against infection and is undergoing phase III clinical trials in Africa with similar efficacy. These findings encouraged us to develop a P. vivax vaccine containing the three circulating allelic forms of P. vivax CSP. Toward this goal, we generated three recombinant bacterial proteins representing the CSP alleles, as well as a hybrid polypeptide called PvCSP-All-CSP-epitopes. This hybrid contains the conserved N and C termini of P. vivax CSP and the three variant repeat domains in tandem. We also generated simian and human recombinant replication-defective adenovirus vectors expressing PvCSP-All-CSP-epitopes. Mice immunized with the mixture of recombinant proteins in a formulation containing the adjuvant poly(I·C) developed high and long-lasting serum IgG titers comparable to those elicited by proteins emulsified in complete Freund's adjuvant. Antibody titers were similar in mice immunized with homologous (protein-protein) and heterologous (adenovirus-protein) vaccine regimens. The antibodies recognized the three allelic forms of CSP, reacted to the repeated and nonrepeated regions of CSP, and recognized sporozoites expressing the alleles VK210 and VK247. The vaccine formulations described in this work should be useful for the further development of an anti-P. vivax vaccine.
机译：间日疟原虫是世界上最普遍和第二大最普遍的引起疟疾的物种。用于控制该疾病传播的当前措施将受益于有效疫苗的开发。以致命的恶性疟原虫为例，含有环子孢子抗原（CSP）的重组RTS，S疫苗可始终保护30％至50％的人类志愿者免受感染，并且正在非洲进行具有类似功效的III期临床试验。这些发现鼓励我们开发一种间日疟原虫疫苗，其中包含间日疟原虫CSP的三种循环等位基因形式。为了实现这一目标，我们生成了代表CSP等位基因的三种重组细菌蛋白，以及称为PvCSP-All-CSP-表位的杂合多肽。该杂种包含间日疟原虫CSP的保守的N和C末端以及串联的三个变体重复结构域。我们还生成了表达PvCSP-All-CSP-表位的猿猴和人重组复制缺陷型腺病毒载体。在含有佐剂聚（I·C）的制剂中用重组蛋白混合物免疫的小鼠产生的高和持久的血清IgG滴度可与完全弗氏佐剂中乳化的蛋白质产生的滴度相当。在用同源（蛋白质-蛋白质）和异源（腺病毒-蛋白质）疫苗接种的小鼠中，抗体滴度相似。抗体识别CSP的三种等位基因形式，与CSP的重复和非重复区域反应，并识别表达等位基因VK210和VK247的子孢子。这项工作中描述的疫苗制剂应可用于抗P的进一步开发。间日间疫苗。

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