Maintaining Robust T Cell Immunity For Broad Protection Against Influenza

摘要：保持强大的T细胞免疫，广泛预防流感 目前使用的流感疫苗主要是为了产生针对外壳蛋白的中和抗体和 必须重新配制，每年给药。它们只有部分有效，而活体感染有很高的疗效。 保护性T细胞介导的免疫，提供多种额外的保护机制，也是至关重要的 用于产生长效中和抗体。 我们最近的研究表明，保护性CD4T细胞免疫的产生需要强烈的病毒呈递 抗原和感染介导的信号持续至少一周。这是因为效应器需要接收 这些信号在明确的检查点期间完成向存储器的过渡。目前的疫苗很少提供 AG或相关病原体识别信号(PR)在如此长的时间内处于最佳水平。此外，人类 反应通常依赖于已经产生的记忆T细胞，并且还不知道记忆CD4T细胞 必须通过类似的检查点才能重新生成第二(20)个内存响应。 在这里，我们将比较灭活全流感产生的记忆CD4T细胞在体内的反应 疫苗与活感染的对比，并确定20个CD4效应者是否同时需要抗原和病原体信号 类似的“效应器检查点”，通过类似的机制，重新生成20个CD4记忆，如果这样的记忆 确实对多种甲型流感病毒提供了强大的异型保护。 如果是这样的话，应该有可能增加疫苗，以在最初和 检查站，这应该为新一代更有效的流感疫苗创造一个框架 它们具有更广泛的保护性，并提供持久的免疫力。此外，同样的策略很可能 可以应用于针对其他病原体的疫苗。

ABSTRACT: Maintaining Robust T Cell Immunity for Broad Protection Against Influenza Influenza vaccines currently in use are designed, primarily to produce neutralizing antibody to coat proteins and must be reformulated and given each year. They are only partially effective, while live infection confers highly protective T cell mediated immunity which provides multiple additional protective mechanisms and also is crucial for generation of long-lasting neutralizing Ab. Our recent studies indicate that generation of protective CD4 T cell immunity requires strong presentation of viral antigen and infection-mediated signals lasting at least a week. This is because the effectors need to receive these signals during a clear-cut checkpoint to complete their transition to memory. Current vaccines rarely supply Ag or the relevant pathogen-recognition signals (PRS) at optimal levels for this long. Moreover, human responses often depend on already generated memory T cells, and it is not known whether memory CD4 T cells must go through a similar checkpoint to re-generate secondary (20) memory responses. Here we will compare the in vivo 20 response of memory CD4 T cells generated by inactivated whole influenza vaccine vs. live infection and determine whether the 20 CD4 effectors also need Ag and pathogen signals at a comparable “effector checkpoint”, via similar mechanisms, to re-generate 20 CD4 memory and if such memory does indeed provide strong heterosubtypic protection against multiple influenza A viruses. If so, it should be possible to augment vaccines to provide the Ag and pathogen signals both initially and at the checkpoint, and this should create a framework for a new generation of more effective vaccines against influenza that are more broadly protective and give long-lasting immunity. Moreover, it is likely that the same strategies could be applied to vaccines against other pathogens.