Live- attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells

• 成果类型: Article
• 署名作者: Chen, Gang; Han, Qingxia; Li, Wan - Xiang; Hai, Rong; Ding, Shou- Wei; Palese, Peter
• 署名单位: University of California System; University of California Riverside
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13710
• DOI: 10.1073/pnas.2321170121
• 发表日期: 2024-04-23
• 关键词: antiviral immunity; influenza-virus; nodamura-virus; interference; proteins; identification; induction; mechanism

摘要

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live - attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito - transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus - targeting small - interfering RNAs. We reported recently that 2 d after immunization with live - attenuated VSR - disabled NoV (NoV A B2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1 -/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi - based protective immunity activated by NoV A B2 immunization. We show that immunization of both neonatal and adult Rag1 -/- mice with live but not killed NoV A B2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoV A B2 - induced protective antiviral immunity is virus - specific and remains effective in adult Rag1 -/- mice 42 and 90 d after a singleshot immunization. We conclude that immunization with the live - attenuated VSR - disabled RNA virus vaccine activates rapid and long - lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity - compromised individuals.