Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan; Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan.
Vaccine. 2017 Dec 4;35(48 Pt B):6620-6626. doi: 10.1016/j.vaccine.2017.10.038. Epub 2017 Nov 1.
The cytotoxic T lymphocyte (CTL) response plays a key role in host recovery from influenza virus infection and in subsequent immunity. Compared to natural infection with influenza virus, however, intranasal vaccination with adjuvant-combined inactivated vaccine elicits only moderate CTL responses. Here we demonstrate that 5 days of consecutive, intranasal vaccination with a combination of inactivated influenza vaccine and poly(I:C) elicits a strong CTL response in the lung. Antigen-captured respiratory DCs did efficiently migrate from the lung to the mediastinal lymph node (mLN) after the 5 day series of inoculations with vaccine and poly(I:C). Importantly, formalin-inactivated whole virus vaccine and poly(I:C) adjuvant have synergic effects on consecutive vaccinations to elicit a strong CTL response in the lung. Although the CTL response was less effective against heterologous influenza virus, we show for the first time that intranasal administration of inactivated influenza virus vaccine and poly(I:C) for 5 consecutive days can elicit high levels of influenza virus-specific CD8 T cells in the lung.
细胞毒性 T 淋巴细胞（CTL）反应在宿主从流感病毒感染中恢复和随后的免疫中起着关键作用。然而，与流感病毒的自然感染相比，用佐剂联合灭活疫苗经鼻内接种仅引起适度的 CTL 反应。在这里，我们证明了用灭活流感疫苗和聚肌苷酸（poly(I:C)）连续 5 天鼻内接种可在肺部引发强烈的 CTL 反应。抗原捕获的呼吸树突状细胞（DC）在接种疫苗和 poly(I:C)的 5 天系列后，有效地从肺部迁移到纵隔淋巴结（mLN）。重要的是，福尔马林灭活的全病毒疫苗和 poly(I:C)佐剂在连续接种中具有协同作用，可在肺部引发强烈的 CTL 反应。尽管 CTL 反应对异源流感病毒的效果较差，但我们首次表明，用灭活流感病毒疫苗和 poly(I:C)连续 5 天经鼻内给药可在肺部引发高水平的流感病毒特异性 CD8 T 细胞。
