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A Tri-Clade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of HPAI H5N1 Viruses

SprMorn 添加于 2012/5/24 15:58:58  1341次阅读 | 0次推荐 | 0个评论

Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds and potential human-to-human transmission, H5N1 influenza viruses remain a major global health concern. High degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. To overcome this, in this study we took a new approach, i.e. development of immunogens based on a comprehensive serologic study. We constructed DNA plasmids encoding codon-optimized HA from 17 representative strains covering all reported clades and subclades of HPAI H5N1 viruses. Using DNA plasmids we generated corresponding H5N1 pseudotypes and immune sera. We performed an across-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. We then designed a tri-clade DNA vaccine and evaluated its immunogenicity and protection in mice. Here we report that (sub)clades 0, 1, 3, 4, 5, 6, 7.1 and 9 were grouped into antigenic cluster 1; (sub)clades 2.1.3.2, 2.3.4, 2.4, 2.5 and 8 into another with subclade 2.2.1 loosely connected to it; and subclades 2.3.2.1 and 7.2 each by itself. Importantly, the tri-clade DNA vaccine encoding HA of (sub)clades 0, 2.3.2.1 and 7.2 elicited broadly neutralizing antibody responses against all H5 clades and subclades and protected mice against high lethal dose heterologous H5N1 challenge. Thus, we conclude that broadly neutralizing antibodies against all H5 clades and subclades can indeed be elicited with immunogens on the basis of a comprehensive serologic study. Further evaluation and optimization of such an approach in ferrets and in humans is warranted

作 者:Fan Zhou1, Guiqing Wang1, Philippe Buchy2, Zhipeng Cai3, Honglin Chen4, Zhiwei Chen5, Genhong Cheng6, Xiu-Feng Wan3, Vincent Deubel2 and Paul Zhou1,*
期刊名称: jv
期卷页: 第卷 第期 页
学科领域:生命科学 » 微生物学 » 病毒学
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原文链接:http://jvi.asm.org/content/early/2012/04/06/JVI.06930-11.abstract?sid=2b228534-c94f-458c-8707-2bf0aa11d082
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相关报道: http://paper.sciencenet.cn/htmlpaper/201252416157324413.shtm
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因为他们的快速发展、遗传多样性、广泛寄主范围、持续的循环在鸟类和潜在的人际传播,H5N1流感病毒依然是一个主要的全球健康问题的关注。高度的遗传多样性也带来了巨大的负担和不确定性在发展中有效的疫苗。为了克服这个问题,在这项研究中我们采用了一种新的方法,即开发基于一个完整的immunogens血清学研究。我们构建了DNA质粒编码codon-optimized公顷从17代表菌株覆盖所有报道的subclades大类和高致病性H5N1病毒。使用DNA质粒生成相应的H5N1 pseudotypes和免疫血清。 我们进行了一pseudotype-based嗣后中和抗原决定簇测定和由制图。然后,我们设计了一个tri-clade DNA疫苗和评估其免疫原性和保护老鼠。我们在这里报告,(子)大类0、1、3、4、5、6、7.1和9被分成抗原集群1;(子)2.1.3.2大类,2.3.4,2.4,2.5,8为另subclade 2.2.1松散连接到它;subclades 2.3.2.1和7.2每个本身。 重要的是,tri-clade DNA疫苗编码公顷(子)大类0,2.3.2.1和7.2引发广泛中和抗体应答反应所有H5型艾滋病毒和subclades和保护小鼠免受高致命剂量异源H5N1的挑战。因此,我们得出结论,具有广泛中和性的抗体对所有H5型艾滋病毒和subclades确实可以与immunogens引出的基础上全面血清学研究。进一步的评估与优化这种做法在雪貂和人类中是有保证的
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