Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens.
Sterile protective immunity to malaria is associated with a panel of novel P. falciparum antigens.
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对疟疾的无菌保护性免疫与一组新型恶性疟原虫抗原有关。
DOI：
10.1074/mcp.m111.007948
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Doolan,DeniseL
中科院分区：
文献类型：
--
作者：
Trieu,Angela;Kayala,MatthewA;Burk,Chad;Molina,DouglasM;Freilich,DanielA;Richie,ThomasL;Baldi,Pierre;Felgner,PhilipL;Doolan,DeniseL
The development of an effective malaria vaccine remains a global public health priority. Less than 0.5% of thePlasmodium falciparumgenome has been assessed as potential vaccine targets and candidate vaccines have been based almost exclusively on single antigens. It is possible that the failure to develop a malaria vaccine despite decades of effort might be attributed to this historic focus. To advance malaria vaccine development, we have fabricated protein microarrays representing 23% of the entireP. falciparumproteome and have probed these arrays with plasma from subjects with sterile protection or no protection after experimental immunization with radiation attenuatedP. falciparumsporozoites. A panel of 19 pre-erythrocytic stage antigens was identified as strongly associated with sporozoite-induced protective immunity; 16 of these antigens were novel and 85% have been independently identified in sporozoite and/or liver stage proteomic or transcriptomic data sets. Reactivity to any individual antigen did not correlate with protection but there was a highly significant difference in the cumulative signal intensity between protected and not protected individuals. Functional annotation indicates that most of these signature proteins are involved in cell cycle/DNA processing and protein synthesis. In addition, 21 novel blood-stage specific antigens were identified. Our data provide the first evidence that sterile protective immunity against malaria is directed against a panel of novelP. falciparumantigens rather than one antigen in isolation. These results have important implications for vaccine development, suggesting that an efficacious malaria vaccine should be multivalent and targeted at a select panel of key antigens, many of which have not been previously characterized.
