Zhao Xiaodong, Chen Fu-Ping, Megaw A George, Sullender Wayne M
Department of Pediatrics, University of Alabama at Birmingham, 1400 6th Avenue S., Birmingham, AL 35233, USA.
J Infect Dis. 2004 Dec 1;190(11):1941-6. doi: 10.1086/425515. Epub 2004 Oct 27.
Palivizumab (PZ) is the only monoclonal antibody in use against a human infectious disease. PZ is given as prophylaxis against infection with respiratory syncytial virus (RSV). An RSV escape mutant, MP4, has been shown to resist PZ prophylaxis in cotton rats.
To further define the potential of RSV to resist prophylaxis, additional PZ-resistant viruses were selected in cell culture and were tested for susceptibility to PZ in cotton rats.
Mutant MS412 had an A-->C mutation at nucleotide position 827 in the F gene, resulting in an amino acid change from Lys to Gln at position 272. Mutant F212 had an A-->T mutation at position 816, leading to an amino acid change from Asn to Ile at position 268. In vitro, F212 had impaired growth kinetics. In cell culture, F212 was partially and MS412 was completely resistant to PZ neutralization. A single prophylactic dose of 15 mg/kg PZ protected cotton rats from infection with F212 but not with MS412.
Both in vitro and in vivo, individual RSV PZ escape mutants varied in their susceptibility to PZ. Mutations associated with resistance to PZ did not always result in failure of PZ prophylaxis.
帕利珠单抗（PZ）是唯一一种用于预防人类传染病的单克隆抗体。PZ用于预防呼吸道合胞病毒（RSV）感染。一种RSV逃逸突变体MP4已被证明在棉鼠中能抵抗PZ预防。
为了进一步确定RSV抵抗预防的可能性，在细胞培养中筛选了更多对PZ耐药的病毒，并在棉鼠中检测它们对PZ的敏感性。
突变体MS412在F基因的核苷酸位置827处发生A→C突变，导致第272位氨基酸从赖氨酸变为谷氨酰胺。突变体F212在位置816处发生A→T突变，导致第268位氨基酸从天冬酰胺变为异亮氨酸。在体外，F212的生长动力学受损。在细胞培养中，F212对PZ中和作用部分耐药，而MS412完全耐药。单剂量15mg/kg的PZ预防可保护棉鼠免受F212感染，但不能预防MS412感染。
无论在体外还是体内，单个RSV PZ逃逸突变体对PZ的敏感性各不相同。与PZ耐药相关的突变并不总是导致PZ预防失败。
