Ledizet Michel, Kar Kalipada, Foellmer Harald G, Bonafé Nathalie, Anthony Karen G, Gould L Hannah, Bushmich Sandra L, Fikrig Erol, Koski Raymond A
L2 Diagnostics, Department of Internal Medicine, Yale School of Medicine, 300 George Street, New Haven, CT 06525, USA.
J Infect Dis. 2007 Dec 15;196(12):1741-8. doi: 10.1086/523654.
The flavivirus envelope (E) protein mediates cellular attachment and fusion with host cell membranes and is recognized by virus-neutralizing antibodies. We raised antibodies against a broad range of epitopes by immunizing a horse with recombinant West Nile virus (WNV) E protein. To define epitopes recognized by protective antibodies, we selected, by affinity chromatography, immunoglobulins against immobilized linear peptides derived from parts of the E protein. Immunoglobulins binding 9 different peptides from domains I, II, and III of the E protein neutralized WNV in vitro. This indicates that multiple protective epitopes can be found in the E protein. Immunoglobulins recognizing 3 peptides derived from domains I and II of E protein protected mice against a lethal challenge with WNV. These immunoglobulins recognized the E proteins of related flaviviruses, demonstrating that antibodies targeting specific E protein epitopes could be developed for prevention and treatment of multiple flavivirus infections.
黄病毒包膜（E）蛋白介导细胞与宿主细胞膜的附着和融合，并被病毒中和抗体识别。我们用重组西尼罗河病毒（WNV）E蛋白免疫一匹马，产生了针对广泛表位的抗体。为了确定保护性抗体识别的表位，我们通过亲和层析从针对固定化的、源自E蛋白部分区域的线性肽的免疫球蛋白中进行筛选。结合E蛋白结构域I、II和III中9种不同肽段的免疫球蛋白在体外可中和WNV。这表明在E蛋白中可发现多个保护性表位。识别源自E蛋白结构域I和II的3种肽段的免疫球蛋白可保护小鼠免受WNV致死性攻击。这些免疫球蛋白可识别相关黄病毒的E蛋白，表明针对特定E蛋白表位的抗体可用于预防和治疗多种黄病毒感染。
