Mutant influenza A virus nucleoprotein is preferentially localized in the cytoplasm and its immunization in mice shows higher immunogenicity and cross-reactivity
Mutant influenza A virus nucleoprotein is preferentially localized in the cytoplasm and its immunization in mice shows higher immunogenicity and cross-reactivity
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DOI：
10.1016/j.vaccine.2007.02.074
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发表时间：
2007-05-22
期刊：
影响因子：
5.5
通讯作者：
Okuda, Keniji
中科院分区：
文献类型：
--
作者：
Ohba, Kenji;Yoshida, Shinsuke;Okuda, Keniji
许多针对血凝素（HA）的流感疫苗显示出有效的免疫原性，可以保护受试者免受流感病毒感染。透明质酸分子的主要抗原变化可帮助流感病毒对以透明质酸为目标的疫苗产生耐药性。编码保守抗原的DNA疫苗保护动物免受多种亚型的侵害，但其效力需要进一步改进。我们利用NP的n端突变体（NPm）高效定位于细胞质中，产生了一种基于DNA的核蛋白（NP）靶向疫苗，并检测了NPm或野生型（WT） NP DNA疫苗免疫小鼠的免疫反应。重要的是，在小鼠中，NPm疫苗的免疫原性比WT NP疫苗高1.5-2倍。此外，接种NPm能有效保护小鼠免受流感病毒的致命攻击，并对异源病毒表现出交叉反应性。因此，NPm基于dna的疫苗接种可能通过其刺激细胞免疫的能力，有助于形成针对多种流感病毒的保护性免疫。(c) 2007 Elsevier Ltd.版权所有。
Many influenza vaccines targeted to hemagglutinin (HA) show efficient immunogenicity for protecting subjects against influenza virus infection. Major antigenic changes to HA molecules can help influenza virus to develop resistance against HA-targeted vaccines. DNA vaccines encoding conserved antigens protect animals against diverse subtypes, but their potency requires further improvement. We generated a DNA-based nucleoprotein (NP)-targeted vaccine using an N-terminal mutant of NP (NPm) that efficiently localized in the cytoplasm, and examined the immune responses in mice immunized with NPm or wild-type (WT) NP DNA vaccine. Importantly, the NPm vaccine showed 1.5-2-fold higher immunogenicity than the WT NP vaccine in mice. Furthermore, NPm vaccination efficiently protected the mice against lethal challenge with influenza viruses and showed cross-reactivity toward heterologous viruses. Therefore, DNA-based vaccination with NPm may contribute to the development of protective immunity against diverse influenza virus through its ability to stimulate cellular immunity. (c) 2007 Elsevier Ltd. All rights reserved.