Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-142 malaria vaccine

Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-142 malaria vaccine
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DOI:
10.1016/s0166-6851(03)00077-x
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发表时间:
2003-05-01
影响因子:
1.5
通讯作者:
Lyon, JA
Lyon, JA
中科院分区:
医学4区
文献类型:
--
作者:
Angov, E;Aufiero, BM;Lyon, JA

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裂殖子表面蛋白-1(42)(MSP-1(42))是针对红细胞疟疾寄生虫的主要候选疫苗。我们在大肠杆菌中克隆并表达了恶性疟原虫MSP-1(42)(3D 7克隆)。通过使用镍-、Q-和羧甲基(CM)-取代的树脂将抗原纯化至大于95%的均一性。最终产品,命名为恶性疟原虫裂殖子蛋白-1(FMP 1),其内毒素水平显著低于FDA标准。基于结合构象依赖性mAb,其结构正确,并且稳定。来自用弗氏佐剂中的FMP 1接种的兔的功能性抗体在体外抑制寄生虫生长,并且还抑制MSP-1的二次加工(42)。用GlaxoSmithKline Biologicals(GSK)佐剂、AS 02 A或明矾配制的FMP 1在恒河猴(Macaca mulatta)中是安全的和免疫原性的。出版社:Elsevier Science B. V.
Merozoite Surface Protein-1(42) (MSP-1(42)) is a leading vaccine candidate against erythrocytic malaria parasites. We cloned and expressed Plasmodium falciparum MSP-1(42) (3D7 clone) in Escherichia coli. The antigen was purified to greater than 95% homogeneity by using nickel-, Q- and carboxy-methyl (CM)-substituted resins. The final product, designated Falciparum Merozoite Protein-1 (FMP1), had endotoxin levels significantly lower than FDA standards. It was structurally correct based on binding conformation-dependent mAbs, and was stable. Functional antibodies from rabbits vaccinated with FMP1 in Freund's adjuvant inhibited parasite growth in vitro and also inhibited secondary processing Of MSP-1(42). FMP1 formulated with GlaxoSmithKline Biologicals (GSK) adjuvant, AS02A or alum was safe and immunogenic in rhesus (Macaca mulatta) monkeys. Published by Elsevier Science B.V.