Anti-class II monoclonal antibody-targeted Vibrio cholerae TcpA pilin: modulation of serologic response, epitope specificity, and isotype.
Anti-class II monoclonal antibody-targeted Vibrio cholerae TcpA pilin: modulation of serologic response, epitope specificity, and isotype.
复制标题
抗 II 类单克隆抗体靶向霍乱弧菌 TcpA 菌毛蛋白：调节血清学反应、表位特异性和同种型。
DOI：
10.1128/iai.69.12.7679-7686.2001
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发表时间：
2001
影响因子：
3.1
通讯作者：
Wade,WF
中科院分区：
文献类型：
--
作者：
Wu,JY;Taylor,RK;Wade,WF
毒素协同调节菌毛（TCP）是霍乱感染所需的定殖因子。当在整个细胞中递送时，它不是一个强大的免疫原，但毛菌亚基或TcpA衍生物合成肽可诱导保护反应。我们检测了用TCP偶联抗II类单克隆抗体（MAb）免疫小鼠的效果，以确定是否可以操纵对TcpA的血清学反应，而不添加霍乱毒素（CT）或抗cd40 MAb。抗ⅱ类单克隆抗体靶向的TCP在效价和同型方面影响了抗TCP肽的血清学反应。ⅱ类单克隆抗体靶向TCP诱导TcpA肽4应答，非靶向TCP诱导TcpA肽4应答。与非靶向TCP应答相比，II类单克隆抗体靶向TcpA降低了对肽6的应答。II类单抗靶向TcpA，如果与CT一起递送，可以增强对TcpA肽的血清学反应。如果在初次免疫中加入抗cd40单抗，则靶向TCP和CT联合的有效性降低。这些数据表明，有必要了解TCP呈递在b细胞表位生成中的作用，以便优化基于TCP的霍乱疫苗。
Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class II MAb-targeted TCP and not with nontargeted TCP. Class II MAb-targeting TcpA reduced the response to peptide 6 compared to the nontargeted TCP response. Class II MAb-targeted TcpA, if delivered with CT, enhanced the serologic response to TcpA peptides. The effectiveness of the combination of targeted TCP and CT was reduced if anti-CD40 MAb were included in the primary immunization. These data establish the need to understand the role of TCP presentation in the generation of B-cell epitopes in order to optimize TcpA-based cholera vaccines.