Induction of broadly neutralizing antibodies against measles virus mutants using a polyepitope vaccine strategy
Induction of broadly neutralizing antibodies against measles virus mutants using a polyepitope vaccine strategy
复制标题
DOI：
10.1016/j.vaccine.2005.01.011
复制
发表时间：
2005-03-18
期刊：
影响因子：
5.5
通讯作者：
Muller, CP
中科院分区：
文献类型：
--
作者：
Bouche, FB;Steinmetz, A;Muller, CP
利用重组技术合成了表达麻疹病毒保护性B细胞表位-血凝素套索表位（命名为“L”aa386-400）多个拷贝的嵌合分子。在转基因胡萝卜植株中产生了重组多聚体[L4T4](2)，该重组多聚体结合了2组4重复的L表位和2组4重复的人破伤风类毒素混杂T细胞表位（“T”，tt830-844）。用植物膜提取物腹腔免疫小鼠后，血清中和了所有野生型病毒。在一项基于cd150转染的Vero细胞抗[L4T4](2)血清的改良斑块减少中和试验中，无论L表位突变如何，血清都能中和所有的field分离株。即使是具有中和性l特异性单克隆抗体接触残基突变或表位其他位置有两个突变的病毒也同样对中和敏感。这些结果表明，L表位的多个拷贝折叠成不同的构象，诱导了足够多样化的B细胞库，以克服野病毒的遗传多样性。(c) 2005 Elsevier Ltd版权所有。
Chimeric molecules expressing multiple copies of the loop-forming hemagglutinin noose epitope (designated as "L" aa386-400), a protective B cell epitope of the measles virus were generated by recombinant technology. The recombinant polyepitope [L4T4](2) combining two sets of four repeats of the L epitope and with two sets of four repeats of the human promiscuous T cell epitope of tetanus toxoid ("T", tt830-844) was produced in transgenic carrot plants. After intraperitoneal immunization of mice with plant membrane extract, sera neutralized all wild-type viruses. In a modified plaque reduction neutralization assay based on CD150-transfected Vero cells anti-[L4T4](2) sera neutralized all field isolates, irrespective of mutations in the L epitope. Even viruses with a mutation in the contact residues of a neutralizing L-specific monoclonal antibody or two mutations in other positions of the epitope were equally sensitive to neutralization. These results suggest that the multiple copies of the L epitope fold into different conformations that induce a repertoire of B cells diverse enough to overcome the genetic diversity of field viruses. (c) 2005 Elsevier Ltd. All rights reserved.