Kitasato Institute for Life Sciences, Laboratory of Viral Infection, Tokyo, Japan.
Vaccine. 2012 Jun 6;30(26):3885-90. doi: 10.1016/j.vaccine.2012.04.004. Epub 2012 Apr 13.
Alum-adjuvanted H5 whole virion inactivated vaccine (WIV) was licensed for adults in Japan but induced marked febrile reactions with significantly stronger antibody responses in children. In this study, the mechanisms behind the different responses were investigated. Lymphocytes were obtained from 25 healthy subjects who were not immunized with H5 vaccine, to examine the innate immune impact of the various vaccine formulations, analyzing the cytokine production profile stimulated with alum adjuvant alone, alum-adjuvanted H5 WIIV, plain H5 WIV, and H5 split vaccine. Alum adjuvant did not induce cytokine production, but H5 split induced IFN-γ and TNF-α. H5 WIV induced IL-6, IL-17, TNF-α, MCP-1, IFN-γ, and IFN-α. An extremely low level of IL-1β was produced in response to H5 WIV, and alum-adjuvanted H5 WIV enhanced IL-1β production, with similar levels of other cytokines stimulated with H5 WIV. Enhanced production of cytokines induced by alum-adjuvanted H5 WIV may be related to the higher incidence of febrile reactions with stronger immune responses in children but it should be further investigated why efficient immune responses with febrile illness were observed only in young children.
日本已批准含佐剂的 H5 全病毒灭活疫苗（WIV）用于成年人，但该疫苗会引起明显的发热反应，且在儿童中产生的抗体反应更强。在这项研究中，研究了不同反应背后的机制。从 25 名未接种过 H5 疫苗的健康受试者中获得淋巴细胞，以研究各种疫苗制剂对固有免疫的影响，分析单独用铝佐剂、铝佐剂 H5 WIIV、普通 H5 WIV 和 H5 裂解疫苗刺激后的细胞因子产生谱。铝佐剂本身不会诱导细胞因子产生，但 H5 裂解会诱导 IFN-γ 和 TNF-α。H5 WIV 诱导产生 IL-6、IL-17、TNF-α、MCP-1、IFN-γ 和 IFN-α。H5 WIV 仅引起极低水平的 IL-1β 产生，而铝佐剂 H5 WIV 增强了 IL-1β 的产生，与用 H5 WIV 刺激产生的其他细胞因子水平相似。铝佐剂 H5 WIV 诱导的细胞因子产生增强可能与儿童发热反应发生率更高和更强的免疫反应有关，但仍需进一步研究为何仅在幼儿中观察到发热性疾病的有效免疫反应。
