Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling
Whole-Virion Influenza Vaccine Recalls an Early Burst of High-Affinity Memory B Cell Response through TLR Signaling
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DOI：
10.4049/jimmunol.1600046
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发表时间：
2016-05-15
影响因子：
4.4
通讯作者：
Takahashi, Yoshimasa
中科院分区：
文献类型：
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作者：
Onodera, Taishi;Hosono, Akira;Takahashi, Yoshimasa
灭活流感疫苗有两种剂型，全病毒体和裂解病毒体类型;然而，不同的剂型如何影响其加强效果仍然未知。在这项研究中，我们证明，全病毒体疫苗召回两波抗体反应，早期T细胞非依赖性（TI）和晚期T细胞依赖性反应，而裂解病毒体疫苗只引起晚期T细胞依赖性反应。值得注意的是，具有改善的中和活性的更高亲和力的Ab由早期TI应答提供，这强调了制剂依赖性应答在保护性免疫中的重要贡献。此外，我们表明，早期TI反应完全需要B细胞内在的TLR 7信号，这可以通过全病毒颗粒疫苗内的病毒RNA传递。因此，我们的结果表明，全病毒体类型的TLR激动剂通过直接靶向记忆B细胞来改善记忆抗体反应，这一发现对旨在迅速回忆高亲和力中和抗体的疫苗策略具有重要意义。
Inactivated influenza vaccines have two formulations, whole-and split-virion types; however, how differential formulations impact their booster effects remain unknown. In this study, we demonstrate that whole-virion vaccines recall two waves of Ab responses, early T cell-independent (TI) and late T cell-dependent responses, whereas split-virion vaccines elicit the late T cell-dependent response only. Notably, higher-affinity Abs with improved neutralizing activity are provided from the early TI response, which emphasizes the important contribution of the formulation-dependent response in the protective immunity. Moreover, we show that the early TI response completely requires B cell-intrinsic TLR7 signaling, which can be delivered through viral RNAs within whole-virion vaccine. Thus, our results indicate that TLR agonists in whole-virion type improve recall Ab responses by directly targeting memory B cells, a finding with important implications for vaccine strategies aimed at the prompt recall of high-affinity neutralizing Abs.