John Sidney, AReum Kim, Rory Dylan de Vries, Bjoern Peters, Philip S. Meade, Florian Krammer, Alba Grifoni, Alessandro Sette
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引用次数: 0
摘要
最近,亚型 H5N1 2.3.4.4b 支系高致病性禽流感(HPAI)病毒频繁扩散到家禽和哺乳动物(尤其是奶牛)中,其中包括几例人类病例,这增加了人们对未来可能发生大流行的担忧。在此,我们对免疫表位数据库(IEDB)中收集的表位数据进行了分析。我们发现,在人类中流行的季节性流感病毒和 H5N1 病毒的免疫优势模式相似。我们还进一步得出结论,T 细胞表位中有相当一部分在禽类和季节性序列之间的交叉反应水平上是保守的,我们还进一步通过实验证明了 IEDB 中最主要的 T 细胞表位存在广泛的交叉反应。基于这些观察结果,以及高致病性禽流感和季节性 H1N1 流感病毒中编码的神经氨酸酶(NA)N1 亚型的总体相似性和交叉反应性 1 组 HA 柄反应抗体,我们预计普通人群中存在一定程度的原有免疫力,可减轻人类 H5N1 感染的严重程度。
Targets of influenza Human T cell response are mostly conserved in H5N1
Frequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals, especially dairy cattle, including several human cases, increased concerns over a possible future pandemic. Here, we performed an analysis of epitope data curated in the Immune Epitope Database (IEDB). We found that the patterns of immunodominance of seasonal influenza viruses circulating in humans and H5N1 are similar. We further conclude that a significant fraction of the T cell epitopes is conserved at a level associated with cross-reactivity between avian and seasonal sequences, and we further experimentally demonstrate extensive cross-reactivity in the most dominant T cell epitopes curated in the IEDB. Based on these observations, and the overall similarity of the neuraminidase (NA) N1 subtype encoded in both HPAI and seasonal H1N1 influenza virus as well as cross-reactive group 1 HA stalk-reactive antibodies, we expect that a degree of pre-existing immunity is present in the general human population that could blunt the severity of human H5N1 infections.