Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.
Vaccine. 2012 Jan 17;30(4):803-12. doi: 10.1016/j.vaccine.2011.10.093. Epub 2011 Nov 17.
Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)(3) as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b(+) CD11c(+) DCs and both CD4(+) Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT.
由于 flt3 配体质粒（pFL）和 CpG 寡脱氧核苷酸（ODN）（3）的组合作为树突状细胞（DC）靶向双粘膜佐剂，引发了卵清蛋白特异性分泌型 IgA（S-IgA）抗体（Ab）反应，我们研究了这种双佐剂是否可以在老年小鼠中诱导流感特异性保护免疫。双佐剂加 A/Puerto Rico/8/34（PR8）血凝素（HA）诱导鼻相关淋巴组织、鼻道和颈部淋巴结中更多的 CD11b（+）CD11c（+）树突状细胞和 CD4（+）Th1 和 Th2 型反应。此外，在给予鼻内 PR8 HA 加这种双佐剂的老年和年轻成年小鼠的上呼吸道（URT）中，检测到 PR8 HA 特异性 S-IgA Ab 反应水平增加。因此，当通过鼻内途径用 PR8 病毒攻击小鼠时，给予鼻内疫苗的老年和年轻成年小鼠均完全受到保护。此外，用双佐剂流感疫苗经鼻免疫的 IgA 缺陷小鼠未能提供针对 PR8 攻击的保护。这些结果表明，鼻内双佐剂成功地在年轻成年和老年小鼠中诱导了 PR8 HA 特异性 IgA Ab 反应，这对于预防小鼠 URT 中的流感感染是必要的。
