Vaccine delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity.

Vaccine delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity.
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DOI:
10.1007/s11095-014-1335-1
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发表时间:
2014-09
影响因子:
3.7
通讯作者:
Gill, Harvinder S.
Gill, Harvinder S.
中科院分区:
医学3区
文献类型:
--
作者:
Ma, Yunzhe;Tao, Wenqian;Krebs, Shelly J.;Sutton, William F.;Haigwood, Nancy L.;Gill, Harvinder S.

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本研究的目的是评估使用涂层微针将疫苗递送到口腔中以诱导全身和粘膜免疫应答的可行性。用磺酰罗丹明、卵清蛋白和两种HIV抗原包被针头。将涂覆的微针插入兔的内下唇和舌背表面。组织学用于确认微针插入,并通过分别测量血清中的抗原特异性免疫球蛋白G(IgG)和唾液中的免疫球蛋白A(伊加)来表征全身和粘膜免疫应答。组织的组织学评价表明,涂层微针可穿透唇和舌以递送涂层。使用卵清蛋白作为模型抗原,发现唇和舌是同样免疫原性的接种部位。重要的是,与免疫前唾液相比,两个位点还在唾液中诱导显著的(p < 0.05)分泌伊加。还将基于针头的口腔接种与使用两种HIV抗原(病毒样颗粒和DNA疫苗)的肌内途径进行了比较。基于针头的递送至口腔和肌内途径在血清中表现出相似(p > 0.05)但显著(p < 0.05)的抗原特异性IgG水平。然而,只有基于微针的口腔疫苗接种组刺激唾液中的抗原特异性伊加应答显著更高(p < 0.05),而不是肌内注射。总之,这项研究提供了一种新的方法,使用微针诱导唾液中的全身性IgG和分泌型伊加,并可以提供一个通用的技术,口腔粘膜接种。
The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively. Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p < 0.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p > 0.05) yet significant (p < 0.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p < 0.05) antigen-specific IgA response in saliva, but not intramuscular injection. In conclusion, this study provides a novel method using microneedles to induce systemic IgG and secretory IgA in saliva, and could offer a versatile technique for oral mucosal vaccination.
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