Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4(+) T cells against the swine-origin H1N1 influenza virus.
Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4(+) T cells against the swine-origin H1N1 influenza virus.
复制标题
DOI：
10.1016/j.vaccine.2011.02.019
复制
发表时间：
2011-04-12
期刊：
影响因子：
5.5
通讯作者：
Drake, Donald R., III
中科院分区：
文献类型：
--
作者：
Schanen, Brian C.;De Groot, Anne S.;Moise, L.;Ardito, Matt;McClaine, Elizabeth;Martin, William;Wittman, Vaughan;Warren, William L.;Drake, Donald R., III
2009年春季爆发的新型猪源性H1N1流感让流行病学家、免疫学家和疫苗接种学家大吃一惊，并引发了全球范围内生产数百万剂疫苗以预防这种单一病毒株的大规模努力。特别令人担忧的是，显然缺乏能够引发对这种新型病毒的交叉保护免疫的预先存在的抗体，这加剧了人们对这种毒株将引发一场特别深远和致命的大流行的担忧。鉴于猪源病毒引起的疾病远没有预期的严重，我们假设，在没有交叉反应性体液免疫的情况下，针对交叉保守的T细胞表位的细胞免疫可能在预防H1N1大流行方面发挥了重要作用。在一项已发表的研究中，我们使用免疫信息学方法预测了2008-2009年季节性H1N1疫苗毒株和大流行H1N1(A/California/04/2009)血凝素蛋白之间的一些CD4+T细胞表位保守。在这里，我们提供了使用来自未接触大流行病毒的人类捐赠者的PBMC的生物学研究结果，以证明预先存在的CD4+T细胞可以引发针对大流行H1N1病毒的交叉反应效应器反应。此外，我们的计算工具显示，我们的计算工具在预测随机选择的HLA单倍型捐赠者的CD4+T细胞表位及其依赖于HLA-DRB1的反应谱方面的准确率为80%-90%。结合这些结果，这些结果证实了免疫信息学的力量，以确定广泛反应的CD4+T细胞表位与高灵敏的体外生物检测，以计算机预测验证这些作为一种手段，了解人类细胞免疫，包括交叉保护反应，并定义CD4+T细胞表位的潜在疫苗努力针对未来的流感病毒和其他病原体。
The outbreak of the novel swine-origin H1N1 influenza in the spring of 2009 took epidemiologists, immunologists, and vaccinologists by surprise and galvanized a massive worldwide effort to produce millions of vaccine doses to protect against this single virus strain. Of particular concern was the apparent lack of pre-existing antibody capable of eliciting cross-protective immunity against this novel virus, which fueled fears this strain would trigger a particularly far-reaching and lethal pandemic. Given that disease caused by the swine-origin virus was far less severe than expected, we hypothesized cellular immunity to cross-conserved T cell epitopes might have played a significant role in protecting against the pandemic H1N1 in the absence of cross-reactive humoral immunity. In a published study, we used an immunoinformatics approach to predict a number of CD4+ T cell epitopes are conserved between the 2008–2009 seasonal H1N1 vaccine strain and pandemic H1N1 (A/California/04/2009) hemagglutinin proteins. Here, we provide results from biological studies using PBMCs from human donors not exposed to the pandemic virus to demonstrate that pre-existing CD4+ T cells can elicit cross-reactive effector responses against the pandemic H1N1 virus. As well, we show our computational tools were 80–90% accurate in predicting CD4+ T cell epitopes and their HLA-DRB1-dependent response profiles in donors that were chosen at random for HLA haplotype. Combined, these results confirm the power of coupling immunoinformatics to define broadly reactive CD4+ T cell epitopes with highly sensitive in vitro biological assays to verify these in silico predictions as a means to understand human cellular immunity, including cross-protective responses, and to define CD4+ T cell epitopes for potential vaccination efforts against future influenza viruses and other pathogens.
登录
查看更多内容
影响因子：
5.4
作者：
Ge, Xinhui;Tan, Venus;Kwok, William W.
通讯作者：
Kwok, William W.
影响因子：
--
作者：
Cohen, Tobias;Moise, Leonard;De Groot, Anne S.
通讯作者：
De Groot, Anne S.
影响因子：
11.8
作者：
Gioia, Cristiana;Castilletti, Concetta;Tempestilli, Massimo;Piacentini, Paola;Bordi, Licia;Chiappini, Roberta;Agrati, Chiara;Squarcione, Salvatore;Lppolito, Giuseppe;Puro, Vincenzo;Capobianchi, Maria R.;Poccia, Fabrizio
通讯作者：
Poccia, Fabrizio
影响因子：
5.5
作者：
De Groot, Anne S.;Rivera, Daniel S.;Martin, William
通讯作者：
Martin, William
影响因子：
5.5
作者：
Kreijtz, J. H. C. M.;Bodewes, R.;Rimmelzwaan, G. F.
通讯作者：
Rimmelzwaan, G. F.