Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
J Virol. 2013 Aug;87(15):8591-605. doi: 10.1128/JVI.01081-13. Epub 2013 May 29.
Despite countermeasures against influenza virus that prevent (vaccines) and treat (antivirals) infection, this upper respiratory tract human pathogen remains a global health burden, causing both seasonal epidemics and occasional pandemics. More potent and safe new vaccine technologies would contribute significantly to the battle against influenza and other respiratory infections. Using plasmid-based reverse genetics techniques, we have developed a single-cycle infectious influenza virus (sciIV) with immunoprotective potential. In our sciIV approach, the fourth viral segment, which codes for the receptor-binding and fusion protein hemagglutinin (HA), has been removed. Thus, upon infection of normal cells, although no infectious progeny are produced, the expression of other viral proteins occurs and is immunogenic. Consequently, sciIV is protective against influenza homologous and heterologous viral challenges in a mouse model. Vaccination with sciIV protects in a dose- and replication-dependent manner, which is attributed to both humoral responses and T cells. Safety, immunogenicity, and protection conferred by sciIV vaccination were also demonstrated in ferrets, where this immunization additionally blocked direct and aerosol transmission events. All together, our studies suggest that sciIV may have potential as a broadly protective vaccine against influenza virus.
尽管有针对流感病毒的预防（疫苗）和治疗（抗病毒药物）措施，但这种上呼吸道人类病原体仍然是全球健康负担，导致季节性流行和偶尔的大流行。更有效和安全的新型疫苗技术将对防治流感和其他呼吸道感染做出重大贡献。我们使用基于质粒的反向遗传学技术，开发了具有免疫保护潜力的单周期传染性流感病毒（sciIV）。在我们的 sciIV 方法中，第四个病毒片段，即编码受体结合和融合蛋白血凝素（HA）的片段，已被删除。因此，在正常细胞感染时，尽管不会产生传染性后代，但会发生其他病毒蛋白的表达，并具有免疫原性。因此，sciIV 在小鼠模型中对流感同源和异源病毒的挑战具有保护作用。sciIV 疫苗接种以剂量和复制依赖性的方式提供保护，这归因于体液反应和 T 细胞。在雪貂中也证明了 sciIV 疫苗接种的安全性、免疫原性和保护作用，其中这种免疫接种还阻断了直接和气溶胶传播事件。总而言之，我们的研究表明，sciIV 可能具有作为一种广泛保护流感病毒的疫苗的潜力。
