MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.

MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.
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DOI:
10.1371/journal.pone.0007790
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发表时间:
2009-11-12
期刊:
影响因子:
3.7
通讯作者:
Rimmelzwaan GF
Rimmelzwaan GF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kreijtz JH;Suezer Y;de Mutsert G;van Amerongen G;Schwantes A;van den Brand JM;Fouchier RA;Löwer J;Osterhaus AD;Sutter G;Rimmelzwaan GF

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自2003年以来,人类感染高致病性H5 N1亚型禽流感病毒的报告频繁,导致高发病率和死亡率。人们担心这些病毒会成为大流行,因此需要开发安全有效的疫苗。MVA为基础的H5 N1疫苗已被证明是有效的,当使用两次高剂量的免疫接种。当疫苗制剂的生产量有限时,剂量节省策略将增加可接种疫苗的人数。此外,理想情况下,在单次免疫后诱导保护性免疫。因此,在小鼠中评估了用基于MVA的H5 N1疫苗诱导保护性免疫的最低要求。为此,用递减剂量的表达流感病毒A/Vietnam/1194/04的HA基因的重组MVA对小鼠接种一次或两次。在用同源进化枝1病毒和衍生自进化枝2.1的异源病毒A/Indonesia/5/05攻击感染后,通过评估体重减轻、病毒复制和组织病理学变化来确定保护效力。得出的结论是,基于MVA的疫苗允许显著的剂量节省并提供交叉进化枝保护,在单次免疫后也是如此,这对于H5 N1候选疫苗是有利的特性。
Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.
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