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开发针对恶性疟原虫疟疾的合成疫苗的理论依据。

Rationale for development of a synthetic vaccine against Plasmodium falciparum malaria.

作者信息

Zavala F, Tam J P, Hollingdale M R, Cochrane A H, Quakyi I, Nussenzweig R S, Nussenzweig V

出版信息

Science. 1985 Jun 21;228(4706):1436-40. doi: 10.1126/science.2409595.

DOI:10.1126/science.2409595
PMID:2409595
Abstract

Protective immunity against malaria can be obtained by vaccination with irradiated sporozoites. The protective antigens known as circumsporozoite (CS) proteins, are polypeptides that cover the surface membrane of the parasite. The CS proteins contain species-specific immunodominant epitopes formed by tandem repeated sequences of amino acids. Here it is shown that the dominant epitope of Plasmodium falciparum is contained in the synthetic dodecapeptide Asn-Ala-Asn-Pro-Asn-Ala-Asn-Pro-Asn-Ala-Pro or (NANP)3. Monoclonal antibodies and most or all polyclonal human antibodies to the sporozoites react with (NANP)3, and polyclonal antibodies raised against the synthetic peptide (NANP)3 react with the surface of the parasite and neutralize its infectivity. Since (NANP)3 repeats are present in CS proteins of P. falciparum from many parts of the world, this epitope is a logical target for vaccine development.

摘要

通过用辐照子孢子进行疫苗接种可获得针对疟疾的保护性免疫。被称为环子孢子(CS)蛋白的保护性抗原是覆盖寄生虫表面膜的多肽。CS蛋白包含由氨基酸串联重复序列形成的物种特异性免疫显性表位。本文表明,恶性疟原虫的显性表位包含在合成十二肽天冬酰胺-丙氨酸-天冬酰胺-脯氨酸-天冬酰胺-丙氨酸-天冬酰胺-脯氨酸-天冬酰胺-丙氨酸-脯氨酸或(NANP)3中。针对子孢子的单克隆抗体以及大多数或所有多克隆人抗体都与(NANP)3反应,针对合成肽(NANP)3产生的多克隆抗体与寄生虫表面反应并中和其感染性。由于(NANP)3重复序列存在于来自世界许多地区的恶性疟原虫的CS蛋白中,因此该表位是疫苗开发的合理靶点。

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