An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus.
An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus.
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DOI：
10.1128/mbio.01044-15
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发表时间：
2015-07-21
期刊：
影响因子：
6.4
通讯作者：
Taubenberger JK
中科院分区：
文献类型：
--
作者：
Schwartzman LM;Cathcart AL;Pujanauski LM;Qi L;Kash JC;Taubenberger JK
流感病毒感染是一个全球性的公共卫生问题，每年的流行病和大流行都会对发病率和死亡率产生重大影响。目前预防年度流感的策略是每年开发一种针对特定流行病毒株的新疫苗。由于这些疫苗不太可能针对抗原性不同的毒株或具有新型血凝素（HA）亚型的新大流行病毒提供保护，因此迫切需要针对所有甲型流感病毒提供保护的疫苗，即所谓的“通用”疫苗。在这里，我们表明，小鼠广泛保护免受各种致命的甲型流感病毒感染（94%的总生存接种后）与病毒样颗粒（VLP）疫苗鸡尾酒的挑战。疫苗由单独展示H1、H3、H5或H7 HA的VLP的混合物组成，并且接种疫苗的小鼠在用表达1918 H1、1957 H2和禽H5、H6、H7、H10和H11血凝素亚型的流感病毒攻击后显示出显著的保护。这些实验为开发具有广泛保护性的“通用”流感疫苗提供了一种有希望的实用策略。甲型流感病毒进化的快速和不可预测性要求每年生产新疫苗以匹配流行的毒株。人类感染源自动物的流感病毒可引起暴发，可能与高死亡率有关，此类毒株也可能适应人类，导致未来的大流行。因此，有很大的公共卫生需要创造广泛的保护性或“通用”流感疫苗，其可以预防各种各样的人类和动物甲型流感病毒引起的疾病。在这项研究中，非感染性病毒样颗粒（VLP）疫苗显示出对小鼠中多种甲型流感病毒的显著保护作用，这表明了开发通用流感疫苗的实用策略。
Influenza virus infections are a global public health problem, with a significant impact of morbidity and mortality from both annual epidemics and pandemics. The current strategy for preventing annual influenza is to develop a new vaccine each year against specific circulating virus strains. Because these vaccines are unlikely to protect against an antigenically divergent strain or a new pandemic virus with a novel hemagglutinin (HA) subtype, there is a critical need for vaccines that protect against all influenza A viruses, a so-called “universal” vaccine. Here we show that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections (94% aggregate survival following vaccination) with a virus-like particle (VLP) vaccine cocktail. The vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7 HAs, and vaccinated mice showed significant protection following challenge with influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 hemagglutinin subtypes. These experiments suggest a promising and practical strategy for developing a broadly protective “universal” influenza vaccine. The rapid and unpredictable nature of influenza A virus evolution requires new vaccines to be produced annually to match circulating strains. Human infections with influenza viruses derived from animals can cause outbreaks that may be associated with high mortality, and such strains may also adapt to humans to cause a future pandemic. Thus, there is a large public health need to create broadly protective, or “universal,” influenza vaccines that could prevent disease from a wide variety of human and animal influenza A viruses. In this study, a noninfectious virus-like particle (VLP) vaccine was shown to offer significant protection against a variety of influenza A viruses in mice, suggesting a practical strategy to develop a universal influenza vaccine.