期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：51
页码：E8296-E8305
DOI：10.1073/pnas.1616530113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe yield of vaccine viruses is important from an economic point of view. Even more important, the ability to produce high numbers of vaccine doses under tight timelines may save many lives during a virus outbreak. Applying an approach that we recently used to develop high-yield influenza A virus vaccine candidates, we now developed high-yield vaccine candidates for both influenza B virus lineages circulating in humans. These vaccine virus candidates confer higher yield in commonly used propagation systems for influenza vaccine virus production: that is, embryonated chicken eggs, Madin-Darby canine kidney cells, and African green monkey (Vero) cells. Our vaccine candidates could be used to improve the influenza B virus vaccine production process. The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.
关键词：influenza B virus ; Yamagata lineage ; Victoria lineage ; vaccine ; high-yield
