Abstract
DNA vaccination appears a very attractive approach for inducing immune responses towards the encoded antigen, but studies in large animals and in humans revealed weaknesses of such responses. In this study, we evaluated a new approach based on a new device combining DNA vaccination with electroporation (EP) at the ear pinna site. Under optimal EP conditions, the expression of the DNA encoded antigen and the induced immune responses were considerably increased. Very interestingly, DNA vaccination using EP at the ear pinna induced much stronger cellular immune responses than at the flank skin although antigen expression was similar at both sites. As compared to vaccination at the ear pinna without EP, IFN- but not IL-4 production by splenocytes from immunized mice was significantly enhanced. In contrast, IL-4 but not IFN- production was increased by EP at the flank skin. The vaccination site of the ear pinna combined with EP route even provided therapeutic effects in a mouse tumor model. In conclusion, this study highlights the ear pinna as a privileged site for the induction of strong Th1 polarized cellular immunity against a defined antigen when combining DNA vaccination with EP.
Highlights
IntroductionGenetic immunization using naked DNA [1, 2] offers considerable advantages over conventional vaccines:(i) high stability of plasmid DNA and relative temperature insensitivity making them highly suitable for mass production and easy transportation in both industrialized and developing countries,(ii) low manufacturing costs,(iii) lack of infection risks that are associated with attenuated viral vaccines,(iv) capacity to target multiple antigens (Ags) on one plasmid by inserting several open reading frames from one or more genes and (v) absence of intrinsic immunogenicity allowing successful boost after DNA vaccination without producing a heterologous immune response.It has been shown to be effective and safe for inducing protective immunity in preclinical models of infectious diseases [3,4,5,6], cancer [7,8,9,10] and autoimmune diseases [11,12,13].After over a decade of active research, DNA vaccines are reaching the commercial market with recent approvals of West Nil virus in horses [14], infectious hematopoetic1876-4010/09 necrosis virus in salmon [15] and melanoma in dogs [16,17,18]
We evaluated a new approach based on a new device combining DNA vaccination with electroporation (EP) at the ear pinna site
DNA vaccination using EP at the ear pinna induced much stronger cellular immune responses than at the flank skin antigen expression was similar at both sites
Summary
Genetic immunization using naked DNA [1, 2] offers considerable advantages over conventional vaccines:(i) high stability of plasmid DNA and relative temperature insensitivity making them highly suitable for mass production and easy transportation in both industrialized and developing countries,(ii) low manufacturing costs,(iii) lack of infection risks that are associated with attenuated viral vaccines,(iv) capacity to target multiple antigens (Ags) on one plasmid by inserting several open reading frames from one or more genes and (v) absence of intrinsic immunogenicity allowing successful boost after DNA vaccination without producing a heterologous immune response.It has been shown to be effective and safe for inducing protective immunity in preclinical models of infectious diseases [3,4,5,6], cancer [7,8,9,10] and autoimmune diseases [11,12,13].After over a decade of active research, DNA vaccines are reaching the commercial market with recent approvals of West Nil virus in horses [14], infectious hematopoetic1876-4010/09 necrosis virus in salmon [15] and melanoma in dogs [16,17,18]. Genetic immunization using naked DNA [1, 2] offers considerable advantages over conventional vaccines:. (iv) capacity to target multiple antigens (Ags) on one plasmid by inserting several open reading frames from one or more genes and (v) absence of intrinsic immunogenicity allowing successful boost after DNA vaccination without producing a heterologous immune response. After over a decade of active research, DNA vaccines are reaching the commercial market with recent approvals of West Nil virus in horses [14], infectious hematopoetic. Despite more than 200 clinical trials to date [19], no plasmid DNA products have received approval by FDA for use in humans. Low vaccine dose results in poor Ag expression and reduced immunogenicity [29]
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