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