Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice.

Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice.
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DOI:
10.1016/j.virol.2012.06.003
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发表时间:
2012-10-10
期刊:
影响因子:
3.7
通讯作者:
Taubenberger JK
Taubenberger JK
中科院分区:
医学3区
文献类型:
--
作者:
Easterbrook JD;Schwartzman LM;Gao J;Kash JC;Morens DM;Couzens L;Wan H;Eichelberger MC;Taubenberger JK

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高致病性H5N1流感与2009年大流行(H1N1pdm09)共享相同的神经氨酸酶(NA)亚型,并且交叉反应性NA免疫可以保护免受或减轻致命的H5N1感染。在这项研究中,小鼠感染亚致死剂量的H1N1pdm09或接种疫苗,并加强与病毒样颗粒(VLP)组成的NA和基质蛋白,标准化的NA活性和鼻内给药,然后用致死剂量的HPAI H5N1病毒的挑战。先前感染H1N1pdm09的小鼠在H5N1攻击后存活,在第4天没有检测到病毒或呼吸道病理。用H5N1或H1N1pdm09 NA VLP免疫的小鼠也被完全保护免于死亡,感染性病毒分别减少100倍和10倍,并且肺部病理学减少。不仅引发HA免疫,而且引发NA免疫的人流感疫苗可以提供针对季节性和大流行性病毒出现的增强的保护。
Highly pathogenic H5N1 influenza shares the same neuraminidase (NA) subtype with the 2009 pandemic (H1N1pdm09), and cross-reactive NA immunity might protect against or mitigate lethal H5N1 infection. In this study, mice were either infected with a sublethal dose of H1N1pdm09 or were vaccinated and boosted with virus-like particles (VLP) consisting of the NA and matrix proteins, standardized by NA activity and administered intranasally, and were then challenged with a lethal dose of HPAI H5N1 virus. Mice previously infected with H1N1pdm09 survived H5N1 challenge with no detectable virus or respiratory tract pathology on day 4. Mice immunized with H5N1 or H1N1pdm09 NA VLPs were also fully protected from death, with a 100-fold and 10-fold reduction in infectious virus, respectively, and reduced pathology in the lungs. Human influenza vaccines that elicit not only HA, but also NA immunity may provide enhanced protection against the emergence of seasonal and pandemic viruses.
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