Abstract：
Immune responses to cross-conserved T cell epitopes in novel H1N1 influenza may explain reports of diminished influenza-like illnesses and confirmed infection among older adults, in the absence of cross-reactive humoral immunity, during the 2009 pandemic. These cross-conserved epitopes may prove useful for the development of a universal H1N1 influenza vaccine, therefore, we set out to identify and characterize cross-conserved H1N1 T cell epitopes. An immunoinformatic analysis was conducted using all available pandemic and pre-pandemic HA-H1 and NA-N1 sequences dating back to 1980. Using an approach that balances potential for immunogenicity with conservation, we derived 13 HA and four NA immunogenic consensus sequences (ICS) from a comprehensive analysis of 5,738 HA-H1 and 5,396 NA-N1 sequences. These epitopes were selected because their combined epitope content is representative of greater than 84% of pre-pandemic and pandemic H1N1 influenza strains, their predicted immunogenicity (EpiMatrix) scores were greater than or equal to the 95th percentile of all comparable epitopes, and they were also predicted to be presented by more than four HLA class II archetypal alleles. We confirmed the ability of these peptides to bind in HLA binding assays and to stimulate interferon-γ production in human peripheral blood mononuclear cell cultures. These studies support the selection of the ICS as components of potential group-common H1N1 vaccine candidates and the application of this universal influenza vaccine development approach to other influenza subtypes.
摘要：
新型H1N1流感中对交叉保守T细胞表位的免疫反应可能解释了老年人流感样疾病减少和确诊感染的报道。在缺乏交叉反应性体液免疫的情况下，在2009年大流行期间。这些交叉保守表位可能被证明对通用H1N1流感疫苗的开发有用。因此,我们着手鉴定和表征交叉保守的H1N1T细胞表位。使用可追溯到1980年的所有可用的大流行和大流行前HA-H1和NA-N1序列进行免疫信息学分析。使用一种平衡免疫原性潜力和保守性的方法，我们从5,738个HA-H1和5,396个NA-N1序列的综合分析中得出了13个HA和4个NA免疫原性共有序列(ICS)。选择这些表位是因为它们的组合表位含量代表了超过84%的大流行前和大流行H1N1流感病毒株。它们的预测免疫原性（EpiMatrix）评分大于或等于所有可比表位的第95百分位数，预计它们也会被超过4个HLAII类原型等位基因呈递。我们证实了这些肽在HLA结合测定中的结合能力以及在人外周血单核细胞培养物中刺激干扰素-γ产生的能力。这些研究支持选择ICS作为潜在群体常见H1N1候选疫苗的组成部分，并支持将这种通用流感疫苗开发方法应用于其他流感亚型。
