Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
J Gene Med. 2011 Jan;13(1):60-72. doi: 10.1002/jgm.1536.
In view of the magnitude and severity of outbreaks of the highly pathogenic H5N1 influenza virus (H5N1-HPIV) and the threat to public health, there is an urgent need to develop broad-spectrum prophylactic and therapeutic agents against infection by H5N1-HPIV and other subtypes.
In the present study, we explored the use of LE-PolyICLC, a liposome encapsulated double-stranded RNA, as a possible prophylactic, therapeutic and immune enhancement agent. In a mouse infection model, we showed that the administration of LE-PolyICLC intranasally before or shortly after infection could inhibit virus replication, leading to a significant reduction in pulmonary viral titres and a higher survival rate of infected mice. When used as a molecular adjuvant, LE-PolyICLC significantly enhanced both the humoral and cellular responses elicited by inactivated H5N1 vaccine and augmented the protective efficacy provided by vaccination. Most importantly, the data also demonstrate that LE-PolyICLC could effectively attenuate the development of pulmonary fibrosis during the restoration period at day 14 after H5N1 infection.
Taken together, the data obtained in the present study suggest that strong consideration should be given for the use of LE-PolyICLC as prophylactic and therapeutic agents and also as a vaccination adjuvant to combat highly pathogenic influenza infection and its associated complications such as pulmonary fibrosis.
鉴于高致病性 H5N1 流感病毒（H5N1-HPIV）爆发的规模和严重程度，以及对公众健康的威胁，迫切需要开发针对 H5N1-HPIV 和其他亚型感染的广谱预防和治疗药物。
在本研究中，我们探索了使用 LE-PolyICLC（一种包裹双链 RNA 的脂质体）作为一种可能的预防、治疗和免疫增强剂。在小鼠感染模型中，我们表明在感染前或感染后不久经鼻腔给予 LE-PolyICLC 可以抑制病毒复制，导致肺部病毒滴度显著降低，感染小鼠的存活率更高。当用作分子佐剂时，LE-PolyICLC 可显著增强灭活 H5N1 疫苗引起的体液和细胞反应，并增强疫苗接种提供的保护效果。最重要的是，数据还表明，LE-PolyICLC 可有效减轻 H5N1 感染后第 14 天恢复期间肺纤维化的发展。
综上所述，本研究获得的数据表明，应强烈考虑将 LE-PolyICLC 用作预防和治疗药物，以及作为疫苗佐剂，以对抗高致病性流感感染及其相关并发症，如肺纤维化。
