Natural Immunization Against Malaria: Causal Prophylaxis with Antibiotics
Natural Immunization Against Malaria: Causal Prophylaxis with Antibiotics
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DOI：
10.1126/scitranslmed.3001058
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发表时间：
2010-07-14
影响因子：
17.1
通讯作者：
Borrmann, Steffen
中科院分区：
文献类型：
--
作者：
Friesen, Johannes;Silvie, Olivier;Borrmann, Steffen
疟疾仍然是最普遍的病媒传染病，死亡率最高。目前的抗疟药物战略治愈疟疾或预防感染，但缺乏持续的公共卫生影响，因为它们未能加速获得保护性免疫。我们表明，在传播寄生虫伯氏疟原虫的过程中，抗生素给药可迅速获得长寿命的、生命周期特异性的保护作用，以防止小鼠活子孢子的再感染。抗生素治疗特异性抑制疟原虫肝脏阶段顶质体的生物发生和遗传，导致肝脏阶段持续成熟，但随后未能建立血液阶段感染。这些减毒肝脏期裂殖子从单个子孢子的指数扩增诱导针对疟疾的有效免疫保护。如果在疟疾流行地区的居民中得到证实，使用安全和负担得起的抗生素进行定期预防可能会为无针替代疟疾免疫策略提供一条强大的捷径。
Malaria remains the most prevalent vector-borne infectious disease and has the highest rates of fatality. Current antimalarial drug strategies cure malaria or prevent infections but lack a sustained public health impact because they fail to expedite the acquisition of protective immunity. We show that antibiotic administration during transmission of the parasite Plasmodium berghei results in swift acquisition of long-lived, life cycle-specific protection against reinfection with live sporozoites in mice. Antibiotic treatment specifically inhibits the biogenesis and inheritance of the apicoplast in Plasmodium liver stages, resulting in continued liver-stage maturation but subsequent failure to establish blood-stage infection. Exponential expansion of these attenuated liver-stage merozoites from a single sporozoite induces potent immune protection against malaria. If confirmed in residents of malaria-endemic areas, periodic prophylaxis with safe and affordable antibiotics may offer a powerful shortcut toward a needle-free surrogate malaria immunization strategy.