Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin.

Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin.
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DOI:
10.1016/j.vaccine.2009.07.060
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发表时间:
2009-09-25
期刊:
影响因子:
5.5
通讯作者:
Paessler S
Paessler S
中科院分区:
医学3区
文献类型:
--
作者:
Song L;Zhang Y;Yun NE;Poussard AL;Smith JN;Smith JK;Borisevich V;Linde JJ;Zacks MA;Li H;Kavita U;Reiserova L;Liu X;Dumuren K;Balasubramanian B;Weaver B;Parent J;Umlauf S;Liu G;Huleatt J;Tussey L;Paessler S

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高致病性禽流感(HPAI)在禽类和人类之间的传播是一种持续的威胁,有可能出现大流行性流感毒株。有效的禽流感疫苗的一个主要障碍是许多HPAI毒株的免疫效力普遍较差,加上使用传统方法的制造限制。临床前研究表明,将Toll样受体-5配体鞭毛蛋白与疫苗抗原融合可增强对融合抗原的免疫应答。在这里,我们评估了一组基于鞭毛蛋白的血凝素(HA)球头融合疫苗在近交系小鼠中的免疫原性和有效性。这些疫苗的HA球状头部来自A/越南/1203/04(VN04;H5N1)HA分子。我们发现,用VN04 HA球状头部取代鞭毛蛋白的D3结构域创建了一种高效疫苗,该疫苗能产生保护性的HAI滴度,在致命的挑战模型中保护小鼠免受疾病和死亡的影响。
Transmission of highly pathogenic avian influenza (HPAI) between birds and humans is an ongoing threat that holds potential for the emergence of a pandemic influenza strain. A major barrier to an effective vaccine against avian influenza has been the generally poor immunopotency of many of the HPAI strains coupled with the manufacturing constraints employing conventional methodologies. Fusion of flagellin, a toll-like receptor-5 ligand, to vaccine antigens has been shown to enhance the immune response to the fused antigen in preclinical studies. Here, we have evaluated the immunogenicity and efficacy of a panel of flagellin-based hemagglutinin (HA) globular head fusion vaccines in inbred mice. The HA globular head of these vaccines is derived from the A/Vietnam/1203/04 (VN04; H5N1) HA molecule. We find that replacement of domain D3 of flagellin with the VN04 HA globular head creates a highly effective vaccine that elicits protective HAI titers which protect mice against disease and death in a lethal challenge model.
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