摘　要：流感病毒灭活疫苗通常需要添加佐剂来增强其免疫保护效果。铝佐剂是常用的人用疫苗佐剂，主要诱导Th2型免疫应答。在本研究中，我们将氢氧化铝（Al）佐剂与TLR7/8激动剂R848组成复合佐剂，与流感病毒H7N9灭活疫苗共同免疫小鼠；单次免疫3周后，用致死剂量（20 LD50）的同源病毒攻击小鼠。结果显示，与含单一R848或Al佐剂的疫苗相比较，添加了R848 + Al复合佐剂的疫苗更能提升小鼠的血清特异性IgG抗体和IgG2a抗体亚类的滴度，诱导Th1和Th2型细胞因子分泌及Th1偏向的免疫应答，能为小鼠抗致死量病毒攻击提供更有效的免疫保护。因此，R848+Al复合佐剂系统强于单一的R848或Al 佐剂。本研究对于改良Al佐剂及提高流感灭活疫苗免疫效果具有参考价值。
关键词：R848；氢氧化铝；灭活疫苗；流感病毒
中图分类号：R186                              文献标志码：A                       DOI：10.3969/j.issn.1007-7146.2023.02.009

Abstract: Inactivated influenza virus vaccines usually require adjuvants to enhance their immune protection. Aluminium hydroxide (Al ) adjuvant is commonly used as an adjuvant in human vaccines, mainly inducing Th2 immune response. In this study, Al adjuvant and TLR7/8 agonist R848 were combined to form a complex adjuvant, and its adjuvancity was evaluated in immunization of mice with inactivated influenza virus H7N9 vaccine. Three weeks after a single immunization, mice were attacked with a lethal dose (20 LD50) of homologous virus. The results showed that, compared with vaccine adjuvanted with R848 or Al alone, R848+ Al adjuvanted vaccine enhanced mice higher titers of serum IgG and IgG2a subtype antibodies and induced both Th1 and Th2 cytokines, with a Th1-biased response, and provided potent protection in mice against lethal virus infection. Therefore, the adjuvancity of R848+ Al is superior to that of R848 or Al alone. The study may help to improve Al adjuvancity and immune effects of inactivated influenza vaccines.
Key words: R848; aluminium hydroxide; inactivated vaccine; influenza virus
（Acta Laser Biology Sinica, 2023, 32(2): 170-176）