Genetic control of malaria parasite transmission: Threshold levels for infection in an avian model system

Genetic control of malaria parasite transmission: Threshold levels for infection in an avian model system
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DOI:
10.4269/ajtmh.2007.76.1072
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发表时间:
2007-06-01
影响因子:
3.3
通讯作者:
James, Anthony A.
James, Anthony A.
中科院分区:
医学4区
文献类型:
--
作者:
Jasinskiene, Nijole;Coleman, Judy;James, Anthony A.

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控制疟疾传播的遗传策略的基础上,工程病原体抗性按蚊正在测试中的一些动物模型。一个关键的组成部分是效应分子和它减少寄生虫传播的效率。单链抗体(scFv),结合环子孢子蛋白的禽寄生虫,鸡疟原虫,可以减少平均强度的子孢子感染的唾液腺由两个到四个数量级的转基因埃及伊蚊。值得注意的是,在其唾液腺中具有少至20个子孢子的蚊子对脊椎动物宿主原鸡(Gallus gallus)具有感染性。尽管scFv有望成为效应分子,但它们必须将感染的平均强度降低到零,以防止寄生虫传播和疾病。我们的结论是,如果我们希望对疾病传播产生影响,人类病原体必须达到类似的终点。
Genetic strategies for controlling malaria transmission based on engineering pathogen resistance in Anopheles mosquitoes are being tested in a number of animal models. A key component is the effector molecule and the efficiency with which it reduces parasite transmission. Single-chain antibodies (scFvs) that bind the circumsporozoite protein of the avian parasite, Plasmodium gallinaceum, can reduce mean intensities of sporozoite infection of salivary glands by two to four orders of magnitude in transgenic Aedes aegypti. Significantly, mosquitoes with as few as 20 sporozoites in their salivary glands are infectious for a vertebrate host, Gallus gallus. Although scFvs hold promise as effector molecules, they will have to reduce mean intensities of infection to zero to prevent parasite transmission and disease. We conclude that similar endpoints must be reached with human pathogens if we are to expect an effect on disease transmission.