Chemical attenuation of Plasmodium berghei sporozoites induces sterile immunity in mice.
Chemical attenuation of Plasmodium berghei sporozoites induces sterile immunity in mice.
复制标题
伯氏疟原虫子孢子的化学减毒可诱导小鼠的无菌免疫。
DOI:
10.1128/iai.01399-07
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发表时间:
2008
影响因子:
3.1
通讯作者:
Rodriguez,Ana
中科院分区:
文献类型:
--
作者:
Purcell,LisaA;Yanow,StephanieK;Lee,Moses;Spithill,TerryW;Rodriguez,Ana
Radiation and genetic attenuation ofPlasmodiumsporozoites are two approaches for whole-organism vaccines that protect against malaria. We evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibitsPlasmodium falciparumgrowth in vitro. Here we show that treatment ofPlasmodium bergheisporozoites with centanamycin impaired parasite function both in vitro and in vivo. The infection of hepatocytes by sporozoites in vitro was significantly reduced, and treated parasites showed arrested liver stage development. Inoculation of mice with sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and C57BL/6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild-type sporozoites. Our findings demonstrate that chemically attenuated sporozoites could be a viable alternative for the production of an effective liver stage vaccine for malaria.