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J Invest Dermatol. 2014 Apr 8. doi: 10.1038/jid.2014.174. [Epub ahead of print]
Co-Localization of Cell Death with Antigen Deposition in Skin Enhances Vaccine Immunogenicity.
Depelsenaire AC1, Meliga SC1, McNeilly CL1, Pearson FE1, Coffey JW1, Haigh OL1, Flaim CJ1, Frazer IH2, Kendall MA3.
Author information
Abstract
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 (i.m.) or intradermal (i.d.) injection. However, the mechanisms behind 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 (~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 ~1-10 MPa. Nanopatch-immunized groups also yielded consistently higher anti-IgG endpoint titers (up to 50-fold higher) than i.d. groups after delivery of a split virion influenza vaccine. Importantly, co-localization 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.Journal of Investigative Dermatology accepted article peview online, 08 April 2014; doi:10.1038/jid.2014.174.
PMID:
24714201
[PubMed - as supplied by publisher]
Co-Localization of Cell Death with Antigen Deposition in Skin Enhances Vaccine Immunogenicity.
Depelsenaire AC1, Meliga SC1, McNeilly CL1, Pearson FE1, Coffey JW1, Haigh OL1, Flaim CJ1, Frazer IH2, Kendall MA3.
Author information
Abstract
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 (i.m.) or intradermal (i.d.) injection. However, the mechanisms behind 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 (~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 ~1-10 MPa. Nanopatch-immunized groups also yielded consistently higher anti-IgG endpoint titers (up to 50-fold higher) than i.d. groups after delivery of a split virion influenza vaccine. Importantly, co-localization 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.Journal of Investigative Dermatology accepted article peview online, 08 April 2014; doi:10.1038/jid.2014.174.
PMID:
24714201
[PubMed - as supplied by publisher]
