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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25
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Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25

机译：Pfs25蛋白偶联物在小鼠中诱发的抗恶性疟原虫抗体的持久和阻断活性

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摘要

Malaria is a leading cause of morbidity and mortality, estimated to cause > 1 million childhood deaths annually. Plasmodium falciparum causes the most severe form of the disease. There is as yet no licensed vaccine for this disease, despite over a half century of research. In this study, we investigated a transmission-blocking vaccine candidate, the ookinete surface protein Pfs25. Antibodies against Pfs25, drawn in during a bite, can block parasite development in the mosquito midgut, preventing transmission to other individuals. Pfs25 is a low-molecular-weight protein, by itself not immunogenic. To increase its immunogenicity, we investigated several methods of conjugating Pfs25 to itself and to other proteins: recombinant Pseudomonas aeruginosa exotoxin A, and ovalbumin, using amide, hydrazone, or thioether linkages. All conjugates were immunogenic and induced booster responses in mice. The scheme to form amide bonds between proteins by using adipic acid dihydrizide as a linker produced the most immunogenic conjugates. Adsorption of the conjugates onto aluminum hydroxide further increased the antibody response. Remarkably, the antibody levels 3 or 7 months after the last injection were significantly higher than those 1 wk after that injection. The observed transmission-blocking activity of immune sera correlated with antibody levels measured by ELISA.
机译：疟疾是发病率和死亡率的主要原因，据估计每年导致超过100万儿童死亡。恶性疟原虫引起该病的最严重形式。尽管进行了半个多世纪的研究，但仍没有针对这种疾病的许可疫苗。在这项研究中，我们研究了一种可阻断传播的疫苗，即人参表面蛋白Pfs25。叮咬期间吸入的针对Pfs25的抗体可以阻止蚊子中肠内的寄生虫发育，从而阻止其传播给其他人。 Pfs25是一种低分子量蛋白，本身不具有免疫原性。为了提高其免疫原性，我们研究了使用酰胺，或硫醚键将Pfs25与自身和其他蛋白质结合的几种方法：重组铜绿假单胞菌外毒素A和卵清蛋白。所有缀合物都是免疫原性的，并在小鼠中诱导了加强反应。通过使用己二酸二氢肼作为连接物在蛋白质之间形成酰胺键的方案产生了最具免疫原性的结合物。缀合物在氢氧化铝上的吸附进一步增加了抗体应答。值得注意的是，最后一次注射后3或7个月的抗体水平明显高于该次注射后1周的抗体水平。观察到的免疫血清的传递阻断活性与通过ELISA测量的抗体水平相关。

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