In vivo selection of respiratory syncytial viruses resistant to monoclonal antibody prophylaxis

ZHAO Xiaodong

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In vivo selection of respiratory syncytial viruses resistant to monoclonal antibody prophylaxis

更新时间：2024-01-17

- In vivo selection of respiratory syncytial viruses resistant to monoclonal antibody prophylaxis
- Journal of Chongqing Medical University Issue 1, Pages: 5-9(2006)
- 作者机构：
  
  1. 重庆医科大学附属儿童医院肾脏免疫科
  2. 重庆医科大学附属儿童医院肾脏免疫科,重庆,400014
- 作者简介：
- 基金信息：
- DOI：
  CLC： R392.1
- Published：2006，
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[1]赵晓东,W.Sullender,杨锡强.呼吸道合胞病毒单克隆抗体抵抗株的体内筛选[J].重庆医科大学学报,2006(01):5-9+18.

ZHAO Xiaodong. In vivo selection of respiratory syncytial viruses resistant to monoclonal antibody prophylaxis. [J]. Journal of Chongqing Medical University (1):5-9(2006)
[1]赵晓东,W.Sullender,杨锡强.呼吸道合胞病毒单克隆抗体抵抗株的体内筛选[J].重庆医科大学学报,2006(01):5-9+18. DOI：

ZHAO Xiaodong. In vivo selection of respiratory syncytial viruses resistant to monoclonal antibody prophylaxis. [J]. Journal of Chongqing Medical University (1):5-9(2006) DOI：

摘要

目的:Palivizum ab（PZ）是目前唯一用于防治感染性疾病的单克隆抗体药物

主要用于预防高危患儿RSV感染。体外筛选获得的PZ逃逸株F基因发生众多突变

且在棉鼠体内完全抵抗大剂量PZ预防效应。本研究评估RSV PZ逃逸株在动物体内是否出现。方法:用环磷酰胺（CY）腹腔注射法制备免疫抑制棉鼠模型

鼻腔接种病毒前24h或后6周肌注15m g/kg PZ。感染后12周收集棉鼠肺脏

用逆转录PCR法扩增RSV F基因片断并克隆入质粒载体

测定克隆cDNA序列筛查F基因突变。结果:在5只接受PZ预防或治疗的棉鼠中

3只棉鼠肺内病毒为含有逃逸株和原型株的混合群体;来自上述3只棉鼠的F基因cDNA克隆中

超过50%显示与体外PZ逃逸株相同的F基因突变。从其中1只棉鼠肺脏中分离的病毒抵抗PZ中和效应。结论:RSV在环磷酰胺处理的棉鼠模型肺内复制时间明显延长

在PZ筛选压力存在情况下

PZ逃逸株可在体内产生

并可能导致PZ预防或治疗失效

提示今后有必要在PZ使用人群中长期监控逃逸株是否出现。

Abstract

Objective: Palivizumab(PZ) is the only monoclonal antibody presently available for use in humans against an infectious disease.RSV selected in cell culture for growth in the presence of PZ develops F gene mutations and is resistant to PZ prophylaxis in cotton rats.Here

we evaluated the potential for PZ resistant RSV to arise in vivo.Methods: Cotton rats were immunosuppressed with cyclophosphamide(CY)

administered PZ

and inoculated intranasally with RSV.Lungs were harvested 12 weeks after RSV infection

RT-PCR amplified F gene fragments were cloned into plasmids

and the nucleotide sequences of the cloned cDNAs were determined.Results: Three of the five animals had mixed populations of lung viruses

and over 50% of the clones from the 3 animals revealed F gene mutations associated with resistance to PZ.A virus completely resistant to PZ neutralization was recovered from the lung homogenate of a rat that had received PZ.Conclusion: Prolonged pulmonary replication of RSV in the presence of PZ is followed by the appearance of viruses resistant to PZ.The potential for the development of resistance is a consideration as antibody is used prophylactically against RSV and as passively administered antibody is under development for other infections

including emerging viruses and agents of biodefense.

关键词

呼吸道合胞病毒逃逸株单克隆抗体免疫抑制动物模型

Keywords

respiratory syncytial virusEscape mutantmonoclonal antibodyimmunosuppressionanimal model

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