Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model.

Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model.
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DOI:
10.1016/j.virol.2016.10.027
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发表时间:
2017-01
期刊:
影响因子:
3.7
通讯作者:
Rudenko, Larisa
Rudenko, Larisa
中科院分区:
医学3区
文献类型:
--
作者:
Isakova-Sivak, Irina;Korenkov, Daniil;Smolonogina, Tatiana;Tretiak, Tatiana;Donina, Svetlana;Rekstin, Andrey;Naykhin, Anatoly;Shcherbik, Svetlana;Pearce, Nicholas;Chen, Li-Mei;Bousse, Tatiana;Rudenko, Larisa

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本研究试图通过包括来自野生型病毒而不是主供体病毒(MDV)的核蛋白(NP)来改进现有的减毒活流感疫苗(LAIV)。比较了具有6:2(来自MDV的NP)和5:3(来自野生型病毒的NP)基因组组成的H7N9 LAIV抑制剂的生长特性、在小鼠中诱导体液和细胞免疫应答以及保护小鼠对抗同源和异源攻击病毒的能力。虽然,一般来说,6:2疫苗比5:3疫苗在C57 BL 6小鼠中诱导更大的细胞介导的免疫,但用5:3 LAIV免疫的小鼠更好地保护免受异源攻击。5:3LAIV诱导的CTL对负载有最近流感病毒的NP 366表位的靶细胞也具有更好的体内杀伤活性。通过掺入来自野生型病毒的NP基因来修饰重组疫苗病毒的基因组代表了改善流感疫苗的免疫原性和交叉保护的简单策略。
This study sought to improve an existing live attenuated influenza vaccine (LAIV) by including nucleoprotein (NP) from wild-type virus rather than master donor virus (MDV). H7N9 LAIV reassortants with 6:2 (NP from MDV) and 5:3 (NP from wild-type virus) genome compositions were compared with regard to their growth characteristics, induction of humoral and cellular immune responses in mice, and ability to protect mice against homologous and heterologous challenge viruses. Although, in general, the 6:2 reassortant induced greater cell-mediated immunity in C57BL6 mice than the 5:3 vaccine, mice immunized with the 5:3 LAIV were better protected against heterologous challenge. The 5:3 LAIV-induced CTLs also had better in vivo killing activity against target cells loaded with the NP366 epitope of recent influenza viruses. Modification of the genome of reassortant vaccine viruses by incorporating the NP gene from wild-type viruses represents a simple strategy to improve the immunogenicity and cross-protection of influenza vaccines.
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