NexBio Incorporated, San Diego, California 92121, USA.
J Infect Dis. 2010 Apr 1;201(7):1007-15. doi: 10.1086/651170.
DAS181 (Fludase) is a sialidase fusion protein in clinical development as a broad-spectrum anti-influenza virus (IFV) therapeutic agent. Previous reports by other investigators have raised the concern that desialylation of airway epithelium might increase susceptibility to Streptococcus pneumoniae infection.
To address whether DAS181 would lead to an increased risk of pneumococcal infection, we tested S. pneumoniae colonization after DAS181 treatment of human A549 cells, healthy mice, and mice challenged with a lethal dose of IFV A/PR/8/34 (H1N1) or A/Victoria/3/75 (H3N2), followed by 10(4) cfu of S. pneumoniae (D39) on day 3 or day 7. DAS181 treatment was given 24-48 h after IFV challenge.
DAS181 treatment did not increase S. pneumoniae colonization in vitro or in vivo in healthy animals. In IFV-infected mice, DAS181 prevented pneumonia and significantly prolonged survival and inhibited the IFV titer by > or = 3 logs. None of the treated animals showed enhanced S. pneumoniae colonization of the lung. In addition, opportunistic infections with Citrobacter species or Klebsiella species occurred only in mice receiving vehicle, not in animals treated with DAS181.
These data indicate that DAS181 treatment does not exacerbate secondary bacterial infection in mice. DAS181 may reduce the risk of secondary bacterial infection by inhibiting IFV.
DAS181（Fludase）是一种唾液酸酶融合蛋白，正在临床开发中作为一种广谱抗流感病毒（IFV）治疗药物。其他研究人员的先前报告引起了人们的关注，即气道上皮的去唾液酸化可能会增加肺炎链球菌感染的易感性。
为了解决 DAS181 是否会导致肺炎球菌感染风险增加的问题，我们测试了 DAS181 处理人 A549 细胞、健康小鼠以及用致死剂量的 IFV A/PR/8/34（H1N1）或 A/Victoria/3/75（H3N2）挑战后的小鼠后肺炎链球菌定植情况，然后在第 3 天或第 7 天用 10（4）cfu 的肺炎链球菌（D39）进行接种。DAS181 治疗在 IFV 攻击后 24-48 小时进行。
DAS181 处理在体外或健康动物体内均未增加肺炎链球菌定植。在 IFV 感染的小鼠中，DAS181 可预防肺炎，并显著延长存活时间，将 IFV 滴度抑制 > 或 = 3 对数级。接受治疗的动物均未显示出肺中肺炎链球菌定植增加。此外，只有接受载体治疗的小鼠出现机会性感染大肠埃希菌或肺炎克雷伯菌，而接受 DAS181 治疗的动物则没有。
这些数据表明，DAS181 治疗不会加重小鼠继发性细菌感染。DAS181 可能通过抑制 IFV 降低继发性细菌感染的风险。
