Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population
Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population
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DOI：
10.1073/pnas.0911580106
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发表时间：
2009-12-01
影响因子：
11.1
通讯作者：
Peters, Bjoern
中科院分区：
文献类型：
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作者：
Greenbaum, Jason A.;Kotturi, Maya F.;Peters, Bjoern
对持续爆发的猪源 H1N1 流感病毒 (S-OIV) 的一个主要担忧是，该病毒可能与季节性 H1N1 流感病毒非常不同，以至于人类几乎不存在免疫保护。在这项研究中，我们检查了针对 S-OIV 的预先存在的免疫的分子基础，即先前由循环流感病毒株引发的 T 细胞或 B 细胞/抗体对病毒免疫表位的识别。利用免疫表位数据库的数据，我们发现最近流行的 H1N1 病毒株中存在的 B 细胞表位只有 31% (8/26) 在 S-OIV 中保守，只有 17% (1/6) 在血凝素 (HA) 和神经氨酸酶 (NA) 表面蛋白中保守。相比之下，CD8+T细胞识别的69%（54/78）表位是完全不变的。我们进一步通过实验证明，成年人群中存在一些针对 S-OIV 的记忆 T 细胞免疫，并且这种记忆与针对季节性 H1N1 流感的预先存在的记忆具有相似的程度。由于感染保护是由抗体介导的，因此可能需要基于特定 S-OIV HA 和 NA 蛋白的新疫苗来预防感染。然而，众所周知，T 细胞可以减轻疾病的严重程度。因此，大部分 T 细胞表位的保守性表明，S-OIV 感染的严重程度（由病毒对免疫攻击的敏感性决定）与季节性流感没有太大差异。这些结果与有关人类 S-OIV 相关疾病发病率、严重程度和死亡率的报告一致。
A major concern about the ongoing swine-origin H1N1 influenza virus (S-OIV) outbreak is that the virus may be so different from seasonal H1N1 that little immune protection exists in the human population. In this study, we examined the molecular basis for pre-existing immunity against S-OIV, namely the recognition of viral immune epitopes by T cells or B cells/antibodies that have been previously primed by circulating influenza strains. Using data from the Immune Epitope Database, we found that only 31% (8/26) of B-cell epitopes present in recently circulating H1N1 strains are conserved in the S-OIV, with only 17% (1/6) conserved in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In contrast, 69% (54/78) of the epitopes recognized by CD8(+) T cells are completely invariant. We further demonstrate experimentally that some memory T-cell immunity against S-OIV is present in the adult population and that such memory is of similar magnitude as the pre-existing memory against seasonal H1N1 influenza. Because protection from infection is antibody mediated, a new vaccine based on the specific S-OIV HA and NA proteins is likely to be required to prevent infection. However, T cells are known to blunt disease severity. Therefore, the conservation of a large fraction of T-cell epitopes suggests that the severity of an S-OIV infection, as far as it is determined by susceptibility of the virus to immune attack, would not differ much from that of seasonal flu. These results are consistent with reports about disease incidence, severity, and mortality rates associated with human S-OIV.