Asanuma Hideki, Fujihashi Kohtaro, Miyakoshi Takashi, Yoshikawa Tomoki, Fujita-Yamaguchi Yoko, Kojima Naoya, Nakata Munehiro, Suzuki Yujiro, Tamura Shin-Ichi, Kurata Takeshi, Sata Tetsutaro
Department of Applied Biochemistry, School or Engineering, Tokai University, Kitakaname 1117, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Vaccine. 2007 Sep 28;25(39-40):6975-80. doi: 10.1016/j.vaccine.2007.06.060. Epub 2007 Jul 16.
Immunological memory induced by nasal immunization with adjuvant-combined influenza vaccine was analyzed in different ages and strains of mice. The memory activities were assessed by secondary nasal-wash IgA and serum IgG antibody (Ab) responses and protection against challenge infection with a lethal dose of influenza virus. Mice were primed with 0.1 microg of vaccine and boosted with 0.1 or 1.0 microg vaccine 1 (short-term memory)- or 17 (long-term memory)-months later. Influenza-specific short-term memory responses in young adult BALB/c mice (2-month-old) were significantly higher than those of long-term memory activities in mice boosted at 19 months of age. However, those influenza-specific long-term memory responses provided protective immunity against influenza virus challenge and were higher than short-term memory in aged mice primed at 18-month-old and boosted 1 month later. These results show that the age at which initial nasal immunization is given is critically important in order to induce protective immunity in aged mice. Similar findings were noted in the C3H mouse strain; however, C57BL/6 mice failed to induce influenza-specific immune responses in both young adult and aged mice. These results indicate that low doses of cholera toxin B subunit (supplemented with 0.2% of hole toxin) combined nasal vaccine may required further improvement in order to provide protective immunity in human use.
我们分析了用佐剂联合流感疫苗经鼻腔免疫在不同年龄和品系小鼠中诱导的免疫记忆。通过二次鼻腔冲洗液中的IgA和血清IgG抗体(Ab)反应以及针对致死剂量流感病毒攻击感染的保护作用来评估记忆活性。用0.1微克疫苗对小鼠进行初次免疫,并在1个月(短期记忆)或17个月(长期记忆)后用0.1或1.0微克疫苗进行加强免疫。年轻成年BALB/c小鼠(2个月大)的流感特异性短期记忆反应显著高于19个月大时加强免疫的小鼠的长期记忆活性。然而,那些流感特异性长期记忆反应提供了针对流感病毒攻击的保护性免疫,并且高于18个月大时初次免疫并在1个月后加强免疫的老年小鼠中的短期记忆。这些结果表明,初次鼻腔免疫的年龄对于在老年小鼠中诱导保护性免疫至关重要。在C3H小鼠品系中也观察到了类似的结果;然而,C57BL/6小鼠在年轻成年和老年小鼠中均未能诱导流感特异性免疫反应。这些结果表明,低剂量霍乱毒素B亚基(补充0.2%全毒素)联合鼻腔疫苗可能需要进一步改进,以便在人类使用中提供保护性免疫。