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首页> 美国卫生研究院文献>Infection and Immunity >A Linear Peptide Containing Minimal T- and B-Cell Epitopes of Plasmodium falciparum Circumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge
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A Linear Peptide Containing Minimal T- and B-Cell Epitopes of Plasmodium falciparum Circumsporozoite Protein Elicits Protection against Transgenic Sporozoite Challenge

机译：线性肽包含最小的恶性疟原虫环子孢子蛋白的T和B细胞表位可抗转基因子孢子攻击

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An effective malaria vaccine is needed to address the public health tragedy resulting from the high levels of morbidity and mortality caused by Plasmodium parasites. The first protective immune mechanism identified in the irradiated sporozoite vaccine, the “gold standard” for malaria preerythrocytic vaccines, was sporozoite-neutralizing antibody specific for the repeat region of the surface circumsporozoite (CS) protein. Previous phase I studies demonstrated that a branched peptide containing minimal T- and B-cell epitopes of Plasmodium falciparum CS protein elicited antirepeat antibody and CD4+-T-cell responses comparable to those observed in volunteers immunized with irradiated P. falciparum sporozoites. The current study compares the immunogenicity of linear versus tetrabranched peptides containing the same minimal T- and B-cell epitopes, T1BT*, comprised of a CS-derived universal Th epitope (T*) synthesized in tandem with the T1 and B repeats of P. falciparum CS protein. A simple 48-mer linear synthetic peptide was found to elicit antisporozoite antibody and gamma interferon-secreting T-cell responses comparable to the more complex tetrabranched peptides in inbred strains of mice. The linear peptide was also immunogenic in outbred nonhuman primates (Aotus nancymaae), eliciting antibody titers equivalent to those induced by tetrabranched peptides. Importantly, the 48-mer linear peptide administered in adjuvants suitable for human use elicited antibody-mediated protection against challenge with rodent malaria transgenic sporozoites expressing P. falciparum CS repeats. These findings support further evaluation of linear peptides as economical, safe, and readily produced malaria vaccines for the one-third of the world's population at risk of malaria infection.
机译：需要一种有效的疟疾疫苗来应对由疟原虫寄生虫引起的高发病率和高死亡率所致的公共卫生悲剧。辐照的子孢子疫苗中确定的第一个保护性免疫机制是疟疾前红细胞疫苗的“金标准”，它是对表面环子孢子（CS）蛋白重复区域特异的子孢子中和抗体。之前的第一阶段研究表明，与恶性疟原虫CS蛋白的T细胞和B细胞表位数量最少的支链肽引起的抗重复抗体和CD4 + -T细胞反应与接受放射免疫的志愿者相当恶性疟原虫子孢子。本研究比较了含有相同最小T细胞和B细胞表位T1BT *的线性支链和四支肽的免疫原性，T1BT *由CS衍生的通用Th表位（T *）与P的T1和B重复串联合成恶性疟原虫CS蛋白发现一种简单的48-mer线性合成肽可与近交小鼠品系中更复杂的四支肽相比，引起抗子孢子抗体和γ干扰素分泌的T细胞反应。线性肽在远交非人类灵长类动物中也具有免疫原性，可产生与四支肽诱导的抗体效价相等的抗体效价。重要的是，在适合人类使用的佐剂中施用的48-mer线性肽引发了抗体介导的抗表达恶性疟原虫CS重复的啮齿类疟疾转基因子孢子的攻击。这些发现支持进一步评估线性肽作为经济，安全且易于生产的疟疾疫苗的适用范围，该疫苗适用于世界三分之一的面临疟疾感染风险的人口。

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