Zirong Han , Qianyi Mai , Yangguo Zhao , Xinglai Liu , Mingting Cui , Minchao Li , Yaoqing Chen , Yuelong Shu , Jianhui Gan , Weiqi Pan , Caijun Sun
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引用次数: 0
摘要
季节性流感每年都会给全球公共卫生带来严重危机,理想的流感疫苗应能针对不断变异的毒株提供广泛的保护。与高度灵活的血凝素(HA)相比,越来越多的数据表明神经氨酸酶(NA)可能是对抗流感变异株的潜在靶标。在本研究中,我们设计了一系列基于遗传算法的镶嵌 NA,然后将其克隆到重组 DNA 和复制缺陷水泡性口炎病毒(VSV)载体中,作为新型流感疫苗的候选株。我们的研究结果表明,DNA质粒/VSV增强策略能激发以Th1为主的强NA特异性免疫反应,而传统的灭活流感疫苗则能激发以Th2为主的免疫反应。更重要的是,我们的策略所诱导的超强NA特异性免疫既能对致命的同源流感挑战提供全面保护,也能对异源流感感染提供部分保护。这些发现将为设计以NA为基础的通用疫苗策略来对抗流感变种提供启示。
Mosaic neuraminidase-based vaccine induces antigen-specific T cell responses against homologous and heterologous influenza viruses
Seasonal influenza is an annually severe crisis for global public health, and an ideal influenza vaccine is expected to provide broad protection against constantly drifted strains. Compared to highly flexible hemagglutinin (HA), increasing data have demonstrated that neuraminidase (NA) might be a potential target against influenza variants. In the present study, a series of genetic algorithm-based mosaic NA were designed, and then cloned into recombinant DNA and replication-defective Vesicular Stomatitis Virus (VSV) vector as a novel influenza vaccine candidate. Our Results showed that DNA prime/VSV boost strategy elicited a robust NA-specific Th1-dominated immune response, but the traditional inactivated influenza vaccine elicited a Th2-dominated immune response. More importantly, the superior NA-specific immunity induced by our strategy could confer both a full protection against lethal homologous influenza challenge and a partial protection against heterologous influenza infection. These findings will provide insights on designing NA-based universal vaccine strategy against influenza variants.
期刊介绍:
Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.