Guan Lizheng, Ping Jihui, Lopes Tiago J S, Fan Shufang, Presler Robert, Neumann Gabriele, Kawaoka Yoshihiro
Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI 53711, USA.
Division of Virology, Department of Microbiology and Immunology, International Research Center for Infectious Diseases, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Vaccines (Basel). 2023 Aug 15;11(8):1364. doi: 10.3390/vaccines11081364.
Vaccination is an efficient approach to preventing influenza virus infections. Recently, we developed influenza A and B virus vaccine backbones that increased the yield of several vaccine viruses in Madin-Darby canine kidney (MDCK) and African green monkey kidney (Vero) cells. These vaccine backbones also increased viral replication in embryonated chicken eggs, which are the most frequently used platform for influenza vaccine manufacturing. In this study, to further increase the viral titers in embryonated chicken eggs, we introduced random mutations into the 'internal genes' (i.e., all influenza viral genes except those encoding the hemagglutinin and neuraminidase proteins) of the influenza A virus high-yield virus backbone we developed previously. The randomly mutated viruses were sequentially passaged in embryonated chicken eggs to select variants with increased replicative ability. We identified a candidate that conferred higher influenza virus growth than the high-yield parental virus backbone. Although the observed increases in virus growth may be considered small, they are highly relevant for vaccine manufacturers.
接种疫苗是预防流感病毒感染的有效方法。最近，我们开发了甲型和乙型流感病毒疫苗主干，提高了几种疫苗病毒在马-达二氏犬肾（MDCK）细胞和非洲绿猴肾（Vero）细胞中的产量。这些疫苗主干还提高了流感疫苗生产中最常用的平台——鸡胚中的病毒复制能力。在本研究中，为了进一步提高鸡胚中的病毒滴度，我们将随机突变引入到我们之前开发的甲型流感病毒高产病毒主干的“内部基因”（即除编码血凝素和神经氨酸酶蛋白的基因外的所有流感病毒基因）中。将随机突变的病毒在鸡胚中连续传代，以选择具有增强复制能力的变体。我们鉴定出了一种候选病毒，其赋予的流感病毒生长能力高于高产亲代病毒主干。尽管观察到的病毒生长增加可能被认为较小，但它们对疫苗制造商具有高度相关性。
