Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity.
Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity.
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DOI：
10.1371/journal.ppat.1003207
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发表时间：
2013-03
期刊：
影响因子：
6.7
通讯作者：
Wherry EJ
中科院分区：
文献类型：
--
作者：
Laidlaw BJ;Decman V;Ali MA;Abt MC;Wolf AI;Monticelli LA;Mozdzanowska K;Angelosanto JM;Artis D;Erikson J;Wherry EJ
在美国，流感病毒的季节性流行每年导致约3.6万人死亡。目前针对流感病毒的疫苗可引起包膜糖蛋白特异性抗体反应。然而，高突变率导致新的病毒血清型的出现，这些血清型无法被先前存在的抗体中和。据报道，T淋巴细胞能够通过识别内部更保守的流感病毒蛋白来介导异亚型保护。在这里，我们使用表达LCMV GP33-41表位的重组流感病毒证明，流感病毒特异性CD8+ T细胞和病毒特异性非中和抗体各自在单独赋予异亚型保护性免疫方面相对无效。然而，当结合病毒特异性CD8 T细胞和非中和抗体时，会产生强大的保护性免疫。这种保护性免疫的协同改善至少部分依赖于肺泡巨噬细胞和/或其他肺吞噬细胞。总的来说，我们的研究表明，一种能够同时激发CD8+ T细胞和高度保守的流感蛋白特异性抗体的流感疫苗可能能够在人类中提供异亚型保护，并作为潜在的“通用”疫苗的基础。流感病毒继续对全球健康构成重大威胁，每年在美国造成数千人死亡。这种威胁主要是由于流感病毒具有快速变化的能力，使其能够逃避以前感染或接种疫苗引起的免疫反应。流感病毒的某些内部决定因素在不同的病毒株中基本上是保守的，是潜在的“通用”流感疫苗的有吸引力的目标。在这里，我们证明了可以通过同时启动针对流感病毒保守元件的多个免疫反应臂来获得针对流感病毒的跨亚型保护。这些结果提示了一种新的策略，可能成为能够提供持久保护的通用流感疫苗的主要组成部分。
Seasonal epidemics of influenza virus result in ∼36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential “universal” vaccine. Influenza virus continues to pose a significant risk to global health and is responsible for thousands of deaths each year in the United States. This threat is largely due to the ability of the influenza virus to undergo rapid changes, allowing it to escape from immune responses elicited by previous infections or vaccinations. Certain internal determinants of the influenza virus are largely conserved across different viral strains and represent attractive targets for potential “universal” influenza vaccines. Here, we demonstrated that cross-subtype protection against the influenza virus could be obtained through simultaneous priming of multiple arms of the immune response against conserved elements of the influenza virus. These results suggest a novel strategy that could potentially form a primary component of a universal influenza vaccine capable of providing long-lasting protection.
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DOI：
10.1084/jem.20052237
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jabbari A;Harty JT
通讯作者：
Harty JT
影响因子：
4.4
作者：
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影响因子：
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Liang, Xiaoping
影响因子：
4.4
作者：
Decman, Vilma;Laidlaw, Brian J.;Wherry, E. John
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Wherry, E. John