New rotavirus vaccine platforms using reverse genetics systems

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02663
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49060:Virology-related
• Research Institution: Osaka University
• Principal Investigator: Kobayashi Takeshi 大阪大学, 微生物病研究所, 教授 (90324847)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ワクチン / ロタウイルス / リバースジェネティクス系

Outline of Final Research Achievements

Rotaviruses are a major cause of severe gastroenteritis in infants and young children worldwide and are responsible for approximately 215,000 deaths annually, particularly in developing countries. The objective of this research is to understand how rotaviruses replicate in vitro and cause diseases in vivo using plasmid-based rotavirus reverse genetics systems. We established a plasmid-based reverse genetics system for G4P[8] human rotavirus strain Odelia. Using reverse genetics systems, we recovered a panel of monoreassortant viruses harboring one gene segment from strain Odelia within the simian rotavirus strain SA11 genetic backbone. We also tried to develop a reverse genetics system for murine rotavirus strain EW. Reassortant viruses between strains SA11 and EW generated by the rescue system enabled study of the biological functions of viral gene segments. These systems will provide insight into the molecular mechanisms underlying rotavirus replication and pathogenesis.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

現在、使用されているロタウイルスワクチンにおいては、発展途上国における不十分な防御効果、高額な費用、副反応（腸重積症）等の問題があげられており、次世代ワクチンの開発研究は重要な課題である。これまで有用なリバースジェネティクス系の開発の遅れからロタウイルスの複製機構ならびに病態発現機序の解明は進んでいなかった。本研究成果で開発されたヒトおよびマウスロタウイルス株のリバースジェネティクス系やレポーター遺伝子発現ロタウイルスを用いた研究は新規ワクチン開発や感染伝播、病態発現機序の理解につながると期待される。