HIV blocking antibodies following immunisation with chimaeric peptides coding a short N-terminal sequence of the CCR5 receptor.
HIV blocking antibodies following immunisation with chimaeric peptides coding a short N-terminal sequence of the CCR5 receptor.
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DOI：
10.1016/j.vaccine.2008.08.025
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发表时间：
2008-10-23
期刊：
影响因子：
5.5
通讯作者：
Wright E
中科院分区：
文献类型：
--
作者：
Chain BM;Noursadeghi M;Gardener M;Tsang J;Wright E
趋化因子受体CCR5是许多HIV毒株进入细胞所必需的，它为包括抗体在内的旨在阻止HIV传播的分子提供了潜在的靶点。这项研究探索了一种刺激CCR5抗体的新方法。用编码CCR5 N端短片段的嵌合肽以及破伤风类毒素的一个无关T细胞表位免疫兔子。用这些嵌合体多肽免疫会产生强烈的抗体反应，高度集中在CCR5的N端序列。含有N-末端蛋氨酸的嵌合肽的抗体也识别细胞表面的全长CCR5受体，尽管浓度较高。与完整CCR5结合和与CCR5多肽结合的进一步比较表明，产生的受体特异性抗体只占总抗肽抗体的很小片段。这些发现与假设一致，即在完整受体的背景下，N端肽具有不同于合成肽的结构。最后，该抗体在体外能够阻断HIV对巨噬细胞的感染。因此，这项研究的结果表明，CCR5的N末端片段可能提供潜在的免疫原，用来产生针对该受体的封闭抗体，同时避免包括T细胞自身表位的危险。
The chemokine receptor CCR5 is required for cellular entry by many strains of HIV, and provides a potential target for molecules, including antibodies, designed to block HIV transmission. This study investigates a novel approach to stimulate antibodies to CCR5. Rabbits were immunised with chimaeric peptides which encode a short fragment of the N-terminal sequence of CCR5, as well as an unrelated T cell epitope from Tetanus toxoid. Immunisation with these chimaeric peptides generates a strong antibody response which is highly focused on the N-terminal CCR5 sequence. The antibody to the chimaeric peptide containing an N-terminal methionine also recognises the full length CCR5 receptor on the cell surface, albeit at higher concentrations. Further comparison of binding to intact CCR5 with binding to CCR5 peptide suggest that the receptor specific antibody generated represents a very small fragment of the total anti-peptide antibody. These findings are consistent with the hypothesis that the N-terminal peptide in the context of the intact receptor has a different structure to that of the synthetic peptide. Finally, the antibody was able to block HIV infection of macrophages in vitro. Thus results of this study suggest that N-terminal fragments of CCR5 may provide potential immunogens with which to generate blocking antibodies to this receptor, while avoiding the dangers of including T cell auto-epitopes.
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影响因子：
2.2
作者：
Liu, SQ;Fan, SX;Sun, ZR
通讯作者：
Sun, ZR
影响因子：
56.9
作者：
Gonzalez, E;Kulkarni, H;Ahuja, SK
通讯作者：
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影响因子：
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作者：
HO, PC;MUTCH, DA;RZEPCZYK, CM
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作者：
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DOI：
10.1073/pnas.96.10.5698
发表时间：
1999-05-11
影响因子：
11.1
作者：
Baba, M;Nishimura, O;Fujino, M
通讯作者：
Fujino, M