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一种使用脂质体疫苗佐剂 CAF09b 的新型预防策略可预防流感病毒病。

A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease.

机构信息

Center for Vaccine Research, Statens Serum Institut, 2300 Copenhagen S, Denmark.

Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen S, Denmark.

出版信息

Int J Mol Sci. 2022 Feb 6;23(3):1850. doi: 10.3390/ijms23031850.

Abstract

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

摘要

SARS-CoV-2 大流行引发了一场大规模的健康和社会危机,尽管有效疫苗的快速发展减轻了一些影响。为了为未来的呼吸道病毒大流行做准备,可以使用泛病毒预防措施来控制疫苗批准前的病毒爆发初期。脂质体疫苗佐剂 CAF09b 含有 TLR3 激动剂聚肌苷酸:聚胞苷酸,它可在受影响的组织中诱导 I 型干扰素 (IFN-I) 反应和抗病毒状态。在测试 CAF09b 脂质体作为一种潜在的泛病毒预防措施时,我们观察到,将 CAF09b 脂质体鼻内给予小鼠可导致固有免疫细胞涌入鼻腔和肺部,并上调 IFN-I 相关基因的表达。当 CAF09b 脂质体在挑战用小鼠适应的流感 A/Puerto Rico/8/1934 病毒之前给予时,它可以预防严重疾病,尽管肺部仍可检测到病毒。然而,当 CAF09b 脂质体在流感挑战后给予时,小鼠的疾病进程与对照组相似。总之,CAF09b 可能是一种适合作为流行病毒泛病毒预防治疗的候选药物,但必须在病毒暴露之前给予才能有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f66/8836410/dc3be03cbb1b/ijms-23-01850-g001.jpg

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