Heckert RA, Elankumaran S, Oshop GL, Vakharia VN, et al.
Veterinary immunology and immunopathology. Date of publication 2002 Oct 8;volume 89(1-2):67-81.
1. Vet Immunol Immunopathol. 2002 Oct 8;89(1-2):67-81.
A novel transcutaneous plasmid-dimethylsulfoxide delivery technique for avian
nucleic acid immunization.
Heckert RA(1), Elankumaran S, Oshop GL, Vakharia VN.
Author information:
(1)Virginia-Maryland Regional College of Veterinary Medicine, University of
Maryland, College Park, MD 20742-3711, USA. rh175@umail.umd.edu
In this report, we show that dimethylsulfoxide (DMSO) enhances liposome-mediated
transfection of nucleic acid in chicken macrophage cells and that this could be
exploited for the transcutaneous delivery of naked DNA through the intact skin of
chickens. We found that DMSO enhanced transfection efficiencies of lipofectamine
and polyethyleneimine in HD-11 chicken macrophage cells. Based on this principle,
we showed that transcutaneous delivery of a DNA plasmid-dimethylsulfoxide mixture
(1:1) to untreated skin of chickens results in a wide distribution of the plasmid
in the body. Distribution studies were done using plasmids encoding enhanced
green fluorescent protein (EGFP) reporter gene and a bivalent DNA vaccine coding
for infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV)
immunogenic protein genes. This bivalent vaccine induced mucosal and systemic
immune responses, as evidenced by IgA and IgM production in the tears and serum
of vaccinated chickens. Mucosal immune responses in the tears after topical
vaccination were significantly higher (P < 0.05) than after i.m. delivery of the
same DNA vaccine and were characterized by the absence of an IgG response. The
biodistribution of plasmid indicated that topical delivery with DMSO resulted in
a wide distribution and persistence of the plasmid until 15 weeks post-primary
vaccination. Both delivery methods resulted in insert-specific message being made
in several body tissues, but after topical delivery the virus-specific mRNA could
be detected in the bone marrow of one out of three chickens until 15 weeks
post-primary vaccination. Furthermore, transcutaneous delivery of this DNA
vaccine using DMSO conferred protection from challenge with virulent IBDV (86%
survival) and NDV (86% survival). This novel transcutaneous method of delivery of
a DNA vaccine shows promise as being an easy and effective way to deliver nucleic
acids through intact skin for vaccination or therapeutic purposes.
DOI: 10.1016/s0165-2427(02)00186-1
PMID: 12208052 [Indexed for MEDLINE]
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