Low immunogenicity predicted for emerging avian-origin H7N9: implication for influenza vaccine design.
Low immunogenicity predicted for emerging avian-origin H7N9: implication for influenza vaccine design.
复制标题
DOI：
10.4161/hv.24939
复制
发表时间：
2013-05
影响因子：
4.8
通讯作者：
Martin W
中科院分区：
文献类型：
--
作者：
De Groot AS;Ardito M;Terry F;Levitz L;Ross T;Moise L;Martin W
2013年2月，上海附近出现了一种新的禽流感病毒，到5月初，已造成130多人感染，36人死亡。禽源性H7N9甲型流感的人际传播仅限于少数家庭聚集性传播，但与人感染相关的高死亡率（27%）引起了人们对该病毒可能成为一种重要人类病原体的担忧。欧洲、美国和亚洲的疫苗公司已经开始将H7抗原如血凝素（HA）克隆到标准化的疫苗生产载体中。不幸的是，以前含有H7 ha的疫苗免疫原性很差。我们使用完善的免疫信息学工具分析H7N9蛋白序列，并将其T细胞表位含量与其他流行甲型流感病毒株进行比较，以估计新流感抗原的免疫原性潜力。我们发现，与其他最近流行的流感病毒株相比，来自密切相关的人源性H7N9病毒株的HA蛋白含有较少的T细胞表位，并且T细胞表位与其他流感病毒株的保守性非常有限。本文详细分析了H7N9病毒中T细胞表位的类型和位置，以及它们在其他H7和流行甲型流感毒株（a/ California/07/2009、a/ Victoria/361/2011和a/ Texas/50/2012）中的保守性。基于这一分析，禽源性H7N9 2013似乎是一种“隐形”病毒，能够逃避人类细胞和体液免疫反应。该分析预测，如果H7N9具有大流行的潜力，将迫切需要新的策略来提高这种独特的低免疫原性禽流感病毒株的疫苗免疫原性。
A new avian-origin influenza virus emerged near Shanghai in February 2013, and by the beginning of May it had caused over 130 human infections and 36 deaths. Human-to-human transmission of avian-origin H7N9 influenza A has been limited to a few family clusters, but the high mortality rate (27%) associated with human infection has raised concern about the potential for this virus to become a significant human pathogen. European, American, and Asian vaccine companies have already initiated the process of cloning H7 antigens such as hemagglutinin (HA) into standardized vaccine production vehicles. Unfortunately, previous H7 HA-containing vaccines have been poorly immunogenic. We used well-established immunoinformatics tools to analyze the H7N9 protein sequences and compare their T cell epitope content to other circulating influenza A strains as a means of estimating the immunogenic potential of the new influenza antigen. We found that the HA proteins derived from closely related human-derived H7N9 strains contain fewer T cell epitopes than other recently circulating strains of influenza, and that conservation of T cell epitopes with other strains of influenza was very limited. Here, we provide a detailed accounting of the type and location of T cell epitopes contained in H7N9 and their conservation in other H7 and circulating (A/California/07/2009, A/Victoria/361/2011, and A/Texas/50/2012) influenza A strains. Based on this analysis, avian-origin H7N9 2013 appears to be a “stealth” virus, capable of evading human cellular and humoral immune response. Should H7N9 develop pandemic potential, this analysis predicts that novel strategies for improving vaccine immunogenicity for this unique low-immunogenicity strain of avian-origin influenza will be urgently needed.
登录
查看更多内容
人类感染新型禽源甲型流感 (H7N9) 病毒。
影响因子：
158.5
作者：
Gao, Rongbao;Cao, Bin;Shu, Yuelong
通讯作者：
Shu, Yuelong
影响因子：
120.7
作者：
Thompson, WW;Shay, DK;Fukuda, K
通讯作者：
Fukuda, K
影响因子：
4.8
作者：
De Groot, AS;Bishop, EA;Martin, W
通讯作者：
Martin, W
DOI：
10.1073/pnas.0813390106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Galli, Grazia;Medini, Duccio;Castellino, Flora
通讯作者：
Castellino, Flora
影响因子：
8.6
作者：
Koren, E.;De Groot, A. S.;Martin, W.
通讯作者：
Martin, W.