Enhancing immunogenicity and reducing dose of microparticulated synthetic vaccines:: Single intradermal administration

Enhancing immunogenicity and reducing dose of microparticulated synthetic vaccines:: Single intradermal administration
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DOI:
10.1023/b:pham.0000012159.20895.5b
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发表时间:
2004-01-01
影响因子:
3.7
通讯作者:
Pedraz, JL
Pedraz, JL
中科院分区:
医学3区
文献类型:
--
作者:
Carcaboso, AM;Hernández, RM;Pedraz, JL

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目的。我们的目的是评估聚合物载体将模型合成疫苗释放到皮肤以达到有效激活特异性免疫反应的能力。采用复乳技术制备了多肽-D,L-丙交酯-乙交酯共聚物微球,并将其应用于Balb/c小鼠体内。通过皮内免疫(I.D.)获得的免疫反应(抗体和T细胞激活)皮下(S.C.)测试路线。结果。给小鼠皮下注射相同剂量的载肽微粒。或者身份证。在小鼠中,免疫后的抗肽抗体免疫应答显著增强。注射到皮肤里。我们还可以通过身份识别将抗原的剂量减少10倍。路线,并发现与S.C.获得的抗体反应相似。免疫接种。在最低剂量水平下,IgG2a/IgG1比值升高,IgE产生减少。身份证明。在两种剂量水平下,微粒子均可诱导多肽刺激的脾细胞和淋巴结细胞分泌显著的干扰素-γ,并显著促进脾细胞培养中T细胞的增殖。结果表明,与传统的皮下注射相比,用更低的剂量和获得更强的抗体和T细胞反应,包载多肽的微粒是有效的给药途径。行政管理。
Purpose. Our purpose was to evaluate the ability of a polymeric vehicle to release a model synthetic vaccine to the skin in order to reach a potent activation of the specific immune response.Methods. The peptide-loaded poly-D,L-lactide-co-glycolide acid ( PLGA) microparticles were prepared by a double emulsion technique and administered to Balb/c mice. The immune response (antibody and T cell activation) obtained by the intradermal (i.d.) and the subcutaneous (s.c.) routes was tested.Results. When similar doses of peptide-loaded microparticles were injected s.c. or i.d. in mice, the antipeptide IgG antibody immune response was found to be significantly higher after i.d. injection into the skin. We could also reduce the dose of antigen 10 times by the i.d. route and find a similar antibody response to that obtained by the s.c. immunization. At the lowest i. d. dose level, the IgG2a/IgG1 ratio was also incremented and the IgE production decreased. The i.d. microparticles induced, at both dose levels, a marked IFN-gamma secretion by peptide-stimulated splenocytes and lymph node cells and a significant T cell proliferation in spleen cell cultures.Conclusions. The results demonstrate that peptide-loaded microparticles were efficiently administered by the i. d. route because lower doses were required and powerful antibody and T cell responses were obtained compared to the conventional s.c. administration.