Induction of pneumococcal polysaccharide-specific mucosal immune responses by oral immunization.

Induction of pneumococcal polysaccharide-specific mucosal immune responses by oral immunization.
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通过口服免疫诱导肺炎球菌多糖特异性粘膜免疫反应。

DOI:
10.1016/0264-410x(95)00198-a
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发表时间:
1996
期刊:
影响因子:
5.5
通讯作者:
Kiyono,H
Kiyono,H
中科院分区:
医学3区
文献类型:
--
作者:
VanCott,JL;Kobayashi,T;Yamamoto,M;Pillai,S;McGhee,JR;Kiyono,H

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脂质体和霍乱毒素(CT)被认为是粘膜疫苗的有效抗原载体和佐剂。在这项研究中,这些抗原递送系统对粘膜给药的肺炎球菌多糖(Pnup)的佐剂应答的影响进行了研究。用纯化的Pnup型23 F制剂对小鼠进行粘膜(例如口服)和全身(IP)免疫接种均诱导血清中的抗原特异性IgM应答。有趣的是,低至10 μg Pnup 23 F型的口服免疫足以诱导全身性IgM应答。Pnup特异性IgM抗体在第7天达到峰值,在第14天第二次给药后没有明显的加强应答。为了检查粘膜免疫是否诱导IgG和伊加Pnup特异性免疫应答,将粘膜佐剂CT与Pnup 23型混合作为口服疫苗。CT和Pnup 23F型的共同口服给药导致Pnup特异性粪便伊加抗体的诱导。这些结果通过检测从免疫小鼠的肠制备的单核细胞悬液中的抗原特异性IgA斑点形成细胞来证实。这些发现表明,在粘膜佐剂如CT存在下用Pnup口服免疫可以诱导Pnup特异性伊加应答,而单独的Pnup则不能。为了进一步增强抗原特异性抗体应答,将Pnup 23 F型包封在脂质体中并用作粘膜疫苗。然而,Pnup的免疫原性并未得到改善。
Liposome and cholera toxin (CT) are considered to be effective antigen delivery vehicles and adjuvants for mucosal vaccines. The effect of these antigen delivery systems on adjuvant responses to mucosally administered pneumococcal polysaccharide (Pnup) was investigated in this study. Both mucosal (e.g. oral) and systemic (IP) immunization of mice with purified preparations of Pnup type 23F induced antigen-specific IgM responses in sera. Interestingly, oral immunization of as little as 10 μg of Pnup type 23F was sufficient to induce systemic IgM responses. Pnup-specific IgM antibodies peaked by day 7 and no booster responses were evident after a second dose on day 14. In order to examine whether IgG and IgA Pnup-specific immune responses are induced by mucosal immunization, the mucosal adjuvant CT was mixed with Pnup type 23 as an oral vaccine. Co-oral administration of CT and Pnup type 23F resulted in the induction of Pnup-specific faecal IgA antibodies. These results were confirmed by detecting antigen-specific IgA-spot-forming cells in mononuclear cell suspensions prepared from the intestine of immunized mice. These findings suggest that oral immunization with Pnup in the presence of mucosal adjuvants, such as CT, could induce Pnup-specific IgA responses whereas Pnup alone did not. In an attempt to further enhance antigen-specific antibody responses, Pnup type 23F was encapsulated in liposomes and used as mucosal vaccine. However, immunogenicity of Pnup was not improved.