期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 51, 页码 E8296-E8305出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1616530113
关键词
influenza B virus; Yamagata lineage; Victoria lineage; vaccine; high-yield
资金
- National Institute of Allergy and Infectious Diseases [HHSN272201400008C]
- Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [16H06429, 16K21723, 16H06434]
- Strategic Basic Research Program of the Japan Science and Technology Agency
- Leading Advanced Projects for medical innovation from the Japan Agency for Medical Research and Development
- Grants-in-Aid for Scientific Research [16H06434] Funding Source: KAKEN
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.
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