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February 2003, Volume 10, Number 3, Pages 251-260 |
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Research Article |
| Enabling topical immunization
via microporation: a novel method for pain-free and needle-free
delivery of adenovirus-based vaccines |
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| J Bramson1, K Dayball1, C Evelegh1,
Y H Wan1, D Page2 and A Smith3 |
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| 1Department of Pathology and
Molecular Medicine, Center for Gene Therapeutics, McMaster
University, Hamilton, Ontario, Canada
2Elan Pharmaceutical Technologies,
Trinity College, Dublin, Ireland
3Altea Genomics, Inc., Atlanta,
GA, USA |
| Correspondence to: Dr J Bramson,
Department of Pathology and Molecular Medicine, McMaster
University, Room HSC-4H21B, 1200 Main Street West, Hamilton,
Ontario L8N 3Z5, Canada |
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Abstract |
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The skin represents an excellent site for vaccine inoculation
due to its natural role as a first line of contact with foreign
pathogens and the high local frequency of antigen presenting
cells. To facilitate skin-directed immunization, a new technique
has been developed (termed microporation) whereby a vaporization
process is used to remove tiny areas of the stratum corneum
creating microscopic pores that allow access to the underlying
viable epidermis. Reporter gene expression was 100-fold
increased following application of an adenovirus vector to
microporated skin when compared to intact skin. Furthermore, 10-100-fold
greater cellular and humoral immune responses were observed
following topical administration of an adenovirus vaccine to
microporated skin versus intact skin. Hairless mice responded to
the microporated adenovirus vaccine equivalently to mice with
normal hair follicle distribution demonstrating the activity of
the microporated vaccine was not related to follicle count. In a
tumor challenge model using a surrogate antigen, microporation
increased vaccine efficacy by approximately 100-fold compared to
intact skin. Finally, microporation enabled delivery of an
adenovirus vaccine carrying a relevant melanoma antigen
resulting in the development of auto-immune vitiligo and tumor
protection. Thus, the microporation technology has proven to be
a reliable and easy method to enable skin-directed vaccination.
Gene Therapy (2003) 10, 251-260.
doi:10.1038/sj.gt.3301886 |
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Keywords |
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| skin; topical immunization; genetic vaccine |
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| Received 8 May 2002; accepted 29
July 2002 |
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February 2003, Volume 10, Number 3, Pages 251-260 |
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