Daffis Stephane, Kontermann Roland E, Korimbocus Jehanara, Zeller Hervé, Klenk Hans-Dieter, Ter Meulen Jan
Institut für Virologie, Philipps-Universität, Robert-Koch-Strasse 17, 35037 Marburg, Germany.
Virology. 2005 Jul 5;337(2):262-72. doi: 10.1016/j.virol.2005.04.031.
Human monoclonal antibody fragments neutralizing wild-type and vaccine strains of yellow fever (YF) virus (genotypes West Africa I + II, East/Central Africa, 17D-204-WHO) were generated by repertoire cloning from YF patients. Analysis of virus escape variants identified amino acid (aa) 71 in domain II of the envelope glycoprotein (E) as the most critical residue for neutralization, with aa 153-155 in domain I contributing to the epitope. These data confirm the previous mapping of YFV neutralizing epitopes using mouse monoclonal antibodies but suggest that a conformational epitope could be formed by amino acids from domains I and II opposing each other in the dimeric form of the E protein. While the sera of the YF patients showed up to 10-fold reduced neutralizing activity against the 17D escape variants, sera from 17D vaccinees retained their neutralizing titers. Mutations in this major neutralizing epitope of YFV thus do not seem to carry the risk of immune escape in persons immunized with the YFV-17D vaccine.
通过对黄热病（YF）患者的抗体库进行克隆，获得了可中和野生型和疫苗株黄热病毒（基因型为西非I + II、东非/中非、17D - 204 - WHO）的人源单克隆抗体片段。对病毒逃逸变异株的分析表明，包膜糖蛋白（E）结构域II中的第71位氨基酸（aa）是中和作用最关键的残基，结构域I中的第153 - 155位氨基酸对表位有贡献。这些数据证实了先前使用小鼠单克隆抗体对黄热病毒中和表位的定位，但表明在E蛋白的二聚体形式中，结构域I和结构域II中相互对立的氨基酸可能形成一个构象表位。虽然黄热病患者的血清对17D逃逸变异株的中和活性降低了多达10倍，但17D疫苗接种者的血清仍保持其中和滴度。因此，黄热病毒这一主要中和表位的突变似乎不会给接种YFV - 17D疫苗的人带来免疫逃逸风险。
