Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA.
J Virol. 2013 May;87(9):5118-27. doi: 10.1128/JVI.02490-12. Epub 2013 Feb 28.
H5N1 and H9N2 avian influenza virus subtypes top the World Health Organization's list for the greatest pandemic potential. Inactivated H5N1 vaccines induce limited immune responses and, in the case of live-attenuated influenza virus vaccines (LAIV), there are safety concerns regarding the possibility of reassortment between the H5 gene segment and circulating influenza viruses. In order to overcome these drawbacks, we rearranged the genome of an avian H9N2 influenza virus and expressed the entire H5 hemagglutinin open reading frame (ORF) from the segment 8 viral RNA. These vectors had reduced polymerase activities as well as viral replication in vitro and excellent safety profiles in vivo. Immunization with the dual H9-H5 influenza virus resulted in protection against lethal H5N1 challenge in mice and ferrets, and also against a potentially pandemic H9 virus. Our studies demonstrate that rearranging the influenza virus genome has great potential for the development of improved vaccines against influenza virus as well as other pathogens.
H5N1 和 H9N2 禽流感病毒亚型是世界卫生组织（WHO）认为最具大流行潜力的病毒。灭活的 H5N1 疫苗可诱导有限的免疫应答，而对于减毒活流感疫苗（LAIV），人们担心 H5 基因片段与流行的流感病毒之间可能发生重配。为了克服这些缺点，我们对禽流感 H9N2 流感病毒的基因组进行了重排，并从 8 号病毒 RNA 上表达了整个 H5 血凝素开放阅读框（ORF）。这些载体的聚合酶活性以及体外病毒复制能力降低，体内安全性良好。用双重 H9-H5 流感病毒免疫可保护小鼠和雪貂免受致命的 H5N1 挑战，也可预防潜在的大流行 H9 病毒。我们的研究表明，重排流感病毒基因组对于开发针对流感病毒以及其他病原体的改良疫苗具有巨大潜力。
