Duvvuri Venkata R, Duvvuri Bhargavi, Alice Christilda, Wu Gillian E, Gubbay Jonathan B, Wu Jianhong
Centre for Disease Modelling, York Institute of Health Research, Toronto, Canada.
York University, Toronto, Canada.
PLoS One. 2014 Mar 7;9(3):e91273. doi: 10.1371/journal.pone.0091273. eCollection 2014.
In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies. Hence, the assessment of preexisting CD4+ T-cell immunity to conserved epitopes shared between H7N9 and human influenza A viruses (IAV) is critical. A comparative whole proteome-wide immunoinformatics analysis was performed to predict the CD4+ T-cell epitopes that are commonly conserved within the proteome of H7N9 in reference to IAV subtypes (H1N1, H2N2, and H3N2). The CD4+ T-cell epitopes that are commonly conserved (∼ 556) were further screened against the Immune Epitope Database (IEDB) to validate their immunogenic potential. This analysis revealed that 45.5% (253 of 556) epitopes are experimentally proven to induce CD4+ T-cell memory responses. In addition, we also found that 23.3% of CD4+ T-cell epitopes have ≥ 90% of sequence homology with experimentally defined CD8+ T-cell epitopes. We also conducted the population coverage analysis across different ethnicities using commonly conserved CD4+ T-cell epitopes and corresponding HLA-DRB1 alleles. Interestingly, the indigenous populations from Canada, United States, Mexico and Australia exhibited low coverage (28.65% to 45.62%) when compared with other ethnicities (57.77% to 94.84%). In summary, the present analysis demonstrate an evidence on the likely presence of preexisting T-cell immunity in human population and also shed light to understand the potential risk of H7N9 virus among indigenous populations, given their high susceptibility during previous pandemic influenza events. This information is crucial for public health policy, in targeting priority groups for immunization programs.
2013年，中国在人类中发现了一种新型禽流感H7N9病毒。抗原性不同的H7N9表面糖蛋白引发了人们对缺乏交叉保护性中和抗体的担忧。表位特异性的预先存在的T细胞免疫是2009年甲型H1N1流感大流行中的一种保护机制，即使在没有交叉保护性抗体的情况下也是如此。因此，评估对H7N9和人类甲型流感病毒（IAV）共有的保守表位预先存在的CD4+T细胞免疫至关重要。进行了一项比较性的全蛋白质组范围的免疫信息学分析，以预测相对于IAV亚型（H1N1、H2N2和H3N2）在H7N9蛋白质组中通常保守的CD4+T细胞表位。将通常保守的（约556个）CD4+T细胞表位针对免疫表位数据库（IEDB）进行进一步筛选，以验证它们的免疫原性潜力。该分析表明，45.5%（556个中的253个）表位经实验证明可诱导CD4+T细胞记忆反应。此外，我们还发现23.3%的CD4+T细胞表位与经实验确定的CD8+T细胞表位具有≥90%的序列同源性。我们还使用通常保守的CD4+T细胞表位和相应的HLA-DRB1等位基因对不同种族进行了群体覆盖率分析。有趣的是，与其他种族（57.77%至94.84%）相比，来自加拿大、美国、墨西哥和澳大利亚的原住民群体覆盖率较低（28.65%至45.62%）。总之，本分析证明了人群中可能存在预先存在的T细胞免疫的证据，并且鉴于原住民群体在以往流感大流行事件中的高易感性，也有助于了解H7N9病毒在他们中的潜在风险。这些信息对于公共卫生政策确定免疫计划的优先群体至关重要。
