Influenza A viruses possessing type B hemagglutinin and neuraminidase: potential as vaccine components
Influenza A viruses possessing type B hemagglutinin and neuraminidase: potential as vaccine components
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DOI：
10.1016/j.micinf.2004.02.011
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发表时间：
2004-05-01
影响因子：
5.8
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Horimoto, T;Iwatsuki-Horimoto, K;Kawaoka, Y
获得许可的减毒活流感疫苗是A型（H1 N1和H3 N2）和B型疫苗病毒的三价混合物。因此，这些病毒之间的干扰可能会限制它们的复制，影响疫苗的效力。克服该潜在问题的一种方法是在A型疫苗病毒背景中使用具有B型血凝素（HA）和神经氨酸酶（NA）的嵌合病毒。我们先前产生了一种具有嵌合HA的A型病毒，其中A型HA分子的整个胞外域被B型HA分子的胞外域取代，并表明这种病毒保护小鼠免受野生型B病毒的攻击。在这里描述的研究中，我们产生了不仅携带嵌合（A/B）HA，而且还携带全长B NA而不是A型NA的A/B型嵌合病毒，导致在A型病毒的背景下具有B HA和NA胞外域的（A/B）HA/NA嵌合病毒。与野生型A病毒相比，这些（A/B）HA/NA嵌合病毒在细胞培养物和小鼠中均减毒。我们的研究结果可能允许从单一主菌株生产有效的流感活疫苗，为未来流感活疫苗的设计提供模型。(C)2004年，Elsevier SAS。All rights reserved.
A licensed live attenuated influenza vaccine is available as a trivalent mixture of types A (H1N1 and H3N2) and B vaccine viruses. Thus, interference among these viruses could restrict their replication, affecting vaccine efficacy. One approach to overcoming this potential problem is to use a chimeric virus possessing type B hemagglutinin (HA) and neuraminidase (NA) in a type A vaccine virus background. We previously generated a type A virus possessing a chimeric HA in which the entire ectodomain of the type A HA molecule was replaced with that of the type B HA, and showed that this virus protected mice from challenge by a wild-type B virus. In the study described here, we generated type A/B chimeric viruses carrying not only the chimeric (A/B) HA, but also the full-length type B NA instead of the type A NA, resulting in (A/B) HA/NA chimeric viruses possessing type B HA and NA ectodomains in the background of a type A virus. These (A/B) HA/NA chimeric viruses were attenuated in both cell culture and mice as compared with the wild-type A virus. Our findings may allow an effective live influenza vaccine to be produced from a single master strain, providing a model for the design of future live influenza vaccines. (C) 2004 Elsevier SAS. All rights reserved.