Neuraminidase-mediated influenza virus egg growth without hemagglutinin antigenic changes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamada Shinya 東京大学, 医科学研究所, 助教 (90466839)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: インフルエンザ / ワクチン / 抗原性 / H3N2

Outline of Final Research Achievements

Vaccination is one of the major strategies to control influenza. However, upon repeated passaging during vaccine production, H3N2 viruses acquire hemagglutinin (HA) mutations that allow them to recognize egg receptors, resulting in changes in antigenicity. Consequently, the effectiveness of the vaccine is appreciably reduced. Here, we show that mutations in neuraminidase (NA) confer efficient replication in eggs to recent human H3N2 viruses without the acquisition of egg-adaptive HA mutations at the major antigenic sites. The mutant NA allowed viruses to aggregate chicken red blood cells, suggesting the mutant NA serves as a receptor-binding protein in place of HA. The amino acid residues located in major antigenic sites remain unchanged during passages in eggs, demonstrating the potential to generate H3N2 vaccine viruses that would not change HA antigenicity during vaccine production, suggesting a potential new approach for the development of high-efficacy influenza vaccines.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

近年のインフルエンザワクチンは流行株に対する効果的な免疫を誘導できないことが大きな社会問題となっているが、本研究はその問題の解決策になりえるものであり、社会的意義は大きいものと考える。