Combination therapy using monoclonal antibodies against respiratory syncytial virus (RSV) G glycoprotein protects from RSV disease in BALB/c mice.

Combination therapy using monoclonal antibodies against respiratory syncytial virus (RSV) G glycoprotein protects from RSV disease in BALB/c mice.
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DOI:
10.1371/journal.pone.0051485
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Haynes LM
Haynes LM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Caidi H;Harcourt JL;Tripp RA;Anderson LJ;Haynes LM

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控制呼吸道合胞病毒(RSV)的治疗选择有限,因此开发新疗法是当务之急。先前的研究表明,单克隆抗体 (mAb) 与 RSV G 蛋白 (mAb 131-2G) 中央保守区 (CCR) 附近的表位具有反应性,显示出对减少 BALB/c 小鼠肺部炎症 RSV 感染的治疗功效。在这里,我们展示了用与 G 蛋白 CCR 内的表位有反应的 mAb (130-6D) 治疗的 RSV 感染小鼠的保护作用,而用对羧基 G 蛋白表位特异的 mAb 治疗则没有效果。与单独使用任一抗体相比,mAb 130-6D 和 131-2G 联合治疗可显着减少 RSV 相关肺部炎症。结果表明,在 CCR 处或附近发生反应并能阻断 RSV G 蛋白介导的活性的抗 RSV G 蛋白 mAb 可有效预防 RSV 疾病,并且可能是 RSV 治疗的有效策略。
Therapeutic options to control respiratory syncytial virus (RSV) are limited, thus development of new therapeutics is high priority. Previous studies with a monoclonal antibody (mAb) reactive to an epitope proximal to the central conserved region (CCR) of RSV G protein (mAb 131-2G) showed therapeutic efficacy for reducing pulmonary inflammation RSV infection in BALB/c mice. Here, we show a protective effect in RSV-infected mice therapeutically treated with a mAb (130-6D) reactive to an epitope within the CCR of G protein, while treatment with a mAb specific for a carboxyl G protein epitope had no effect. Combined treatment with mAbs 130-6D and 131-2G significantly decreased RSV-associated pulmonary inflammation compared to either antibody alone. The results suggest that anti-RSV G protein mAbs that react at or near the CCR and can block RSV G protein-mediated activities are effective at preventing RSV disease and may be an effective strategy for RSV therapeutic treatment.
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