期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 134, 期 9, 页码 2361-2370出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2014.174
关键词
-
类别
资金
- ARC [LP130100882, DP130100996]
- NHMRC of Australia [APP11049906]
- NIH [5U01-CA141583]
- Australian Research Council [LP130100882] Funding Source: Australian Research Council
Vaccines delivered to the skin by microneedles-with and without adjuvants-have increased immunogenicity with lower doses than standard vaccine delivery techniques such as intramuscular or intradermal injection. However, the mechanisms underlying this skin-mediated adjuvant effect are not clear. Here, we show that the dynamic application of a microprojection array (the Nanopatch) to skin generates localized transient stresses invoking cell death around each projection. Nanopatch application caused significantly higher levels (similar to 65-fold) of cell death in murine ear skin than i.d. injection using a hypodermic needle. Measured skin cell death is associated with modeled stresses similar to 1-10 MPa. Nanopatch-immunized groups also yielded consistently higher anti-immunoglobulin G endpoint titers (up to 50-fold higher) than i.d. groups after delivery of a split virion influenza vaccine. Importantly, colocalization of cell death with nearby live skin cells and delivered antigen was necessary for immunogenicity enhancement. These results suggest a correlation between cell death caused by the Nanopatch with increased immunogenicity. We propose that the localized cell death serves as a physical immune enhancer for the adjacent viable skin cells, which also receive antigen from the projections. This natural immune enhancer effect has the potential to mitigate or replace chemical-based adjuvants in vaccines.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据