Crowe J E, Cheung P Y, Wallace E F, Chanock R M, Larrick J W, Murphy B R, Fry K
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Clin Diagn Lab Immunol. 1994 Nov;1(6):701-6. doi: 10.1128/cdli.1.6.701-706.1994.
Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract disease in infants and young children. In this study a hybridoma line secreting a chimpanzee monoclonal antibody that neutralizes RSV was isolated. Two chimpanzees were immunized with recombinant vaccinia viruses that express the RSV F or G surface glycoprotein and 1 month later were infected intranasally with the wild-type RSV strain A2. Peripheral blood lymphocytes obtained from the animals were transformed with Epstein-Barr virus, and lymphoblastoid cell lines that secreted anti-RSV antibodies were identified by an RSV antigen-binding enzyme-linked immunosorbent assay. Supernatants from RSV antibody-secreting lymphoblastoid cell lines were tested for in vitro virus neutralization before being fused to the heteromyeloma cell GLI-H7. A chimpanzee antibody [immunoglobulin G3(lambda) subclass] produced from a hybridoma line designated E1.4/2 was shown to bind to the RSV G glycoprotein and neutralize a panel of subgroup A viruses, but not subgroup B viruses, at low (nanomolar) concentrations. Mice passively immunized with this antibody were partially resistant to RSV strain A2 challenge. The usefulness of such antibodies in immunoprophylaxis and immunotherapy of RSV infection is discussed.
呼吸道合胞病毒(RSV)是婴幼儿严重下呼吸道疾病的最常见病因。在本研究中,分离出了一株分泌可中和RSV的黑猩猩单克隆抗体的杂交瘤细胞系。用表达RSV F或G表面糖蛋白的重组痘苗病毒免疫两只黑猩猩,1个月后经鼻内接种野生型RSV毒株A2。用爱泼斯坦-巴尔病毒转化从动物获得的外周血淋巴细胞,并通过RSV抗原结合酶联免疫吸附试验鉴定分泌抗RSV抗体的淋巴母细胞系。在与异源骨髓瘤细胞GLI-H7融合之前,检测分泌RSV抗体的淋巴母细胞系的上清液的体外病毒中和能力。由命名为E1.4/2的杂交瘤细胞系产生的一种黑猩猩抗体[免疫球蛋白G3(λ)亚类]显示可与RSV G糖蛋白结合,并在低(纳摩尔)浓度下中和一组A亚组病毒,但不能中和B亚组病毒。用该抗体被动免疫的小鼠对RSV毒株A2攻击具有部分抗性。讨论了此类抗体在RSV感染的免疫预防和免疫治疗中的实用性。