CONSTRUCTION OF SYNTHETIC IMMUNOGEN - USE OF NEW T-HELPER EPITOPE ON MALARIA CIRCUMSPOROZOITE PROTEIN

CONSTRUCTION OF SYNTHETIC IMMUNOGEN - USE OF NEW T-HELPER EPITOPE ON MALARIA CIRCUMSPOROZOITE PROTEIN
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DOI:
10.1126/science.2434994
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发表时间:
1987-02-27
期刊:
影响因子:
56.9
通讯作者:
BERZOFSKY, JA
BERZOFSKY, JA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
GOOD, MF;MALOY, WL;BERZOFSKY, JA

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恶性疟原虫的环子孢子(CS)蛋白是开发抗子孢子疟疾疫苗的重点。在这种分子上定位T细胞识别位点对于疫苗设计至关重要。通过使用设计用于预测T细胞位点的算法和一大组H-2同源小鼠,定位了主要的非重复性T细胞位点。当对应于该位点的合成肽与分子上的主要B细胞位点共价连接时,形成了能够引发高滴度抗体应答的免疫原。该肽序列可以引发辅助性T细胞对完整CS蛋白的次级应答。新的辅助性T细胞位点位于CS蛋白的重复区域之外,并且似乎是分子上的免疫显性T位点。这种方法在疫苗的合理设计和构建中应该是有用的。
The circumsporozoite (CS) protein of Plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell site and a large panel of H-2 congenic mice, a major nonrepetitive T-cell site was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high-titer antibody response was formed. This peptide sequence could prime helper T cells for a secondary response to the intact CS protein. The new helper T-cell site is located outside the repetitive region of the CS protein and appears to be the immunodominant T site on the molecule. This approach should be useful in the rational design and construction of vaccines.