A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging.

A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging.
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DOI:
10.1016/j.vaccine.2011.10.093
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发表时间:
2012-01-17
期刊:
影响因子:
5.5
通讯作者:
Fujihashi, Kohtaro
Fujihashi, Kohtaro
中科院分区:
医学3区
文献类型:
--
作者:
Asanuma, Hideki;Zamri, Normaiza Binti;Sekine, Shinichi;Fukuyama, Yoshiko;Tokuhara, Daisuke;Gilbert, Rebekah S.;Fukuiwa, Tatsuya;Fujihashi, Keiko;Sata, Tetsutaro;Tashiro, Masato;Fujihashi, Kohtaro

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由于flt 3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)靶向的双粘膜佐剂引起卵清蛋白特异性分泌型伊加(S-IgA)抗体(Ab)的反应,我们检查这种双佐剂是否可以诱导流感特异性保护性免疫在老年小鼠。双佐剂加A/波多黎各/8/34(PR 8)-血凝素(HA)诱导鼻咽相关淋巴网状组织、鼻道和颈部淋巴结中CD 11 b + CD 11 c + DC数量增加以及CD 4 + Th 1和Th 2型应答。此外,在给予鼻用PR 8-HA和该双佐剂的老年和年轻成年小鼠的上呼吸道触觉(URT)中检测到PR 8-HA特异性S-IgA Ab应答水平增加。因此,当小鼠通过鼻途径用PR 8病毒攻击时,给予鼻疫苗的老年和年轻成年小鼠均表现出完全保护。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PR 8攻击的保护。这些结果表明,鼻用双佐剂在年轻成年小鼠和老年小鼠中成功诱导PR 8-HA特异性伊加Ab应答,这对于预防鼠URT中的流感感染是必不可少的。
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.
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