Kiseleva I V, Bazhenova E A, Larionova N V, Fedorova E A, Dubrovina I A, Isakova-Sivak I N, Rudenko L G
Vopr Virusol. 2013 Sep-Oct;58(5):26-31.
The live attenuated influenza vaccine (LAIV) currently licensed in Russia consists of the reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments from the circulating wild-type viruses and the six internal protein-encoding gene segments from cold-adapted master donor viruses (MDV) A/Leningrad/134/17/57 (H2N2) or B/USSR/60/69. Presently, only classical reassortment technique is approved for the generation of Russian LAIV strains. In this work, we describe the obstacles to the development of LAIV 6:2 vaccine strains depending on the phenotypic properties of the wild-type viruses used for reassortment. It was demonstrated that the highest percentage of 6:2 vaccine reassortants could be achieved when wild-type parental viruses were resistant to non-specific gamma-inhibitors. It was shown that it was impossible to generate 6:2 vaccine reassortants possessing six internal genes of the AILeningrad113417/57 (H2N2) master donor virus and avian HA and NA genes from H5N1-PR8 viruses using classical reassortment technique. It was suggested that strong constellation effects between the gene segments of the parental viruses could affect the virus gene reassortment. A strong interaction between the genome segments encoding neuraminidase of avian origin and PB2 gene of PR8 virus was observed. When the PB2 gene was inherited from cold-adapted master donor virus, the neuraminidase was also found to be of MDV origin.
俄罗斯目前获批的减毒活流感疫苗（LAIV）由重组病毒组成，其血凝素（HA）和神经氨酸酶（NA）基因片段来自流行的野生型病毒，六个内部蛋白质编码基因片段来自冷适应主供体病毒（MDV）A/列宁格勒/134/17/57（H2N2）或B/苏联/60/69。目前，俄罗斯LAIV毒株的生产仅批准使用经典重组技术。在这项工作中，我们根据用于重组的野生型病毒的表型特性，描述了LAIV 6:2疫苗毒株开发的障碍。结果表明，当野生型亲本病毒对非特异性γ抑制剂耐药时，可获得最高比例的6:2疫苗重组体。结果表明，使用经典重组技术，不可能产生具有AILeningrad113417/57（H2N2）主供体病毒的六个内部基因以及来自H5N1-PR8病毒的禽HA和NA基因的6:2疫苗重组体。研究表明，亲本病毒基因片段之间的强大星座效应可能会影响病毒基因重组。观察到源自禽的神经氨酸酶编码基因片段与PR8病毒的PB2基因之间存在强烈相互作用。当PB2基因从冷适应主供体病毒遗传时，神经氨酸酶也被发现源自MDV。
