Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus.
Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus.
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DOI：
10.4049/jimmunol.1003057
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Kaminski DA
中科院分区：
文献类型：
--
作者：
LaMere MW;Lam HT;Moquin A;Haynes L;Lund FE;Randall TD;Kaminski DA
甲型流感病毒引起反复出现的季节性流行和偶尔的流感大流行。由于包膜糖蛋白Ags的变化，灭活疫苗诱导的中和抗体对新病毒血清型的交叉保护作用有限。然而，先前的流感感染诱导异亚型免疫，加速第二株病毒的清除，即使外部蛋白是不同的。在小鼠中，交叉保护也可以通过用高度保守的内部核蛋白（NP）进行全身免疫来引起。T淋巴细胞和Ab都有助于这种交叉保护。在本文中，我们证明，抗NP IgG特异性地促进流感病毒在小鼠中的清除，通过使用涉及FcRs和CD8+细胞的机制。此外，抗NP IgG挽救了B细胞缺陷小鼠中较差的异亚型免疫，这与增强的NP特异性CD8 T细胞应答相关。因此，针对该保守Ag的Ab在初始受试者和流感免疫受试者中均具有有效的抗病毒活性。当小鼠接种另一种内部流感蛋白非结构1时，没有观察到这种抗病毒活性。NP Ag的高度保守性和Ab应答的已知寿命表明，抗NP IgG可提供通用流感疫苗的急需组分。
Influenza A virus causes recurring seasonal epidemics and occasional influenza pandemics. Because of changes in envelope glycoprotein Ags, neutralizing Abs induced by inactivated vaccines provide limited cross-protection against new viral serotypes. However, prior influenza infection induces heterosubtypic immunity that accelerates viral clearance of a second strain, even if the external proteins are distinct. In mice, cross-protection can also be elicited by systemic immunization with the highly conserved internal nucleoprotein (NP). Both T lymphocytes and Ab contribute to such cross-protection. In this paper, we demonstrate that anti-NP IgG specifically promoted influenza virus clearance in mice by using a mechanism involving both FcRs and CD8+ cells. Furthermore, anti-NP IgG rescued poor heterosubtypic immunity in B cell-deficient mice, correlating with enhanced NP-specific CD8 T cell responses. Thus, Ab against this conserved Ag has potent antiviral activity both in naive and in influenza-immune subjects. Such antiviral activity was not seen when mice were vaccinated with another internal influenza protein, nonstructural 1. The high conservation of NP Ag and the known longevity of Ab responses suggest that anti-NP IgG may provide a critically needed component of a universal influenza vaccine.
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