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首页> 外文期刊>Infection and immunity >Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum.
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Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum.

机译：重组或天然蛋白质保护猴子免受恶性疟原虫异源攻击的能力。

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To circumvent problems associated with polymorphic vaccine candidates for Plasmodium falciparum malaria, we evaluated recombinant proteins representing sequences from relatively high conserved regions of the precursor to the major merozoite surface proteins, gp190, for their ability to protect Saimiri monkeys against malaria challenge. Recombinant proteins represented amino acid residues 147 to 321 (p190-1) or 147 to 321 and 1060 to 1195 (p190-3), and their efficacy was compared with that of native gp190 and its processed products. All antigens were derived from P. falciparum K1, a Thai isolate, while the challenge strain was Palo Alto (from Uganda, Africa), which contains, with the exception of the N-terminal 375 amino acids, which are almost identical to the K1 sequence, essentially the MAD-20 allelic form of gp190. By 12 days following challenge, each control monkey required drug treatment. Three monkeys injected with p190-3 required therapy, while one cleared the parasites without therapy. Two monkeys injected with p190-1 received therapy on day 14, while the remaining two cleared the parasites without therapy. Of four animals injected with native gp190, because of health reasons unrelated to malaria, one was not challenged with parasites and one was removed from the study 8 days after challenge when its parasitemia was 1.1% (parasitemias in control animals ranged from 4.3 to 9%); the remaining two cleared the parasites after maximum parasitemias of 0.45 and 0.53%. The highest levels of antiparasite antibody were produced by animals immunized with native gp190. There was a significant correlation between monkeys which did not require drug treatment and antiparasite antibody. These results may suggest that native gp190 and/or its processed products can provide excellent protection against heterologous challenge and that antibody is important for protection. The challenge for vaccine development is to identify the protective sequence(s).
机译：为了规避与恶性疟原虫疟疾多态性疫苗候选物相关的问题，我们评估了代表从前体的相对较高保守区到主要裂殖子表面蛋白gp190的序列的重组蛋白，它们具有保护Saimiri猴子抵抗疟疾攻击的能力。重组蛋白代表氨基酸残基147至321（p190-1）或147至321和1060至1195（p190-3），并将其功效与天然gp190及其加工产品进行比较。所有抗原均来自泰国分离株恶性疟原虫K1，而攻击菌株为Palo Alto（来自非洲乌干达），除了N末端的375个氨基酸外，其余都与K1相同，其中包含序列，基本上是gp190的MAD-20等位基因形式。攻击后12天，每只对照猴子都需要药物治疗。注射p190-3的三只猴子需要治疗，而一只没有治疗的动物清除了寄生虫。注射p190-1的两只猴子在第14天接受了治疗，其余两只猴子未经治疗清除了寄生虫。在四只注射天然gp190的动物中，由于与疟疾无关的健康原因，其中一只没有受到寄生虫的攻击，另一只在攻击后8天被寄生虫的寄生虫率为1.1％（研究动物的寄生虫率为4.3％至9％）从研究中移除。 ）;在最大寄生率分别为0.45和0.53％之后，其余两个清除了寄生虫。用天然gp190免疫的动物产生了最高水平的抗寄生虫抗体。不需要药物治疗的猴子与抗寄生虫抗体之间存在显着相关性。这些结果可能表明天然gp190和/或其加工产物可以提供优异的针对异源攻击的保护，并且抗体对于保护是重要的。疫苗开发的挑战是确定保护序列。

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