Protection Induced by Plasmodium falciparum MSP142 Is Strain-Specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses
Protection Induced by Plasmodium falciparum MSP142 Is Strain-Specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses
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DOI：
10.1371/journal.pone.0002830
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发表时间：
2008-07-30
期刊：
影响因子：
3.7
通讯作者：
Barnwell, John W.
中科院分区：
文献类型：
--
作者：
Lyon, Jeffrey A.;Angov, Evelina;Barnwell, John W.
接种恶性疟原虫MSP1(42)/完全弗氏佐剂（FA）后再接种MSP1(42)/不完全弗氏佐剂（FA）是唯一已知的保护南毛猴免受红细胞期疟疾寄生虫感染的方案。佐剂的作用尚未明确；但是完全FA不能用于人体。在啮齿动物模型中，免疫是菌株特异性的。我们将大肠杆菌中表达的MSP1（42）的FVO或3D7等位基因或杆状病毒（bv）中表达的FVO等位基因与完整和不完整FA、Montanide ISA-720 （ISA-720）或AS02A联合接种给猕猴。用FVO恶性疟原虫攻毒表明，对累积第11天寄生虫病的抑制是菌株特异性的，可以由表达MSP1（42）的大肠杆菌与FA或ISA-720联合诱导，但不能与AS02A联合诱导。coli42-FVO抗原诱导的保护作用强于bv42-FVO抗原，FA诱导的保护作用强于ISA-720。攻毒日（DOC） ELISA抗体（Ab）应答与第c- 11天寄生虫率呈负相关（r = -0.843）。在DOC中，ELISA抗体水平达到至少115,000个ELISA抗体单位滴度，确定不需要治疗的疫苗接种者（noTx），真阳性率为83.3%，假阳性率为14.3%。功能性生长抑制抗体水平（GIA）与第11天累计寄生虫血症的相关性较弱（r = -0.511），不能作为noTx反应的预测指标。GIA的最低假阳性率为30%，而要求的真阳性率为83.3%。这些抑制结果以及显示抗原/FA组合比抗原/ISA-720或抗原/AS02组合诱导更强的保护性免疫的结果与归因于msp1特异性嗜细胞抗体的保护一致。针对红细胞期恶性疟原虫感染的有效MSP1（42）疫苗的开发不仅取决于抗原质量，还取决于最佳佐剂成分的选择。
Vaccination with Plasmodium falciparum MSP1(42)/complete Freund's adjuvant (FA) followed by MSP1(42)/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP1(42) expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP1(42) in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = -0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3%. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = -0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP1(42) vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component.