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DNA vaccines encoding DEC205-targeted antigens: immunity or tolerance?
- Source :
- Immunology; Aug2015, Vol. 145 Issue 4, p519-533, 15p
- Publication Year :
- 2015
-
Abstract
- Targeting of antigens to the endocytic uptake receptor DEC205 resulted in enhanced antigen presentation by dendritic cells ( DCs). In combination with adjuvants for DC maturation, proteins coupled to an antibody against DEC205 induced strong pathogen-specific immune responses, whereas without additional adjuvant tolerance could be induced. As less is known about DNA vaccines encoding DEC205-targeted antigens, we explored the immunogenicity and efficacy of a dendritic cell-targeted DNA vaccine against influenza A virus ( IAV) delivered by electroporation. Although coupling of haemagglutinin to a single-chain antibody against DEC205 enhanced antigen presentation on MHC class II and activation of T-cell receptor-transgenic CD4 T cells, the T-cell responses induced by the targeted DNA vaccine in wild-type BALB/c mice were significantly reduced compared with DNA encoding non-targeted antigens. Consistently, these mice were less protected against an IAV infection. Adoptive transfer experiments were performed to assess the fate of the antigen-specific T cells in animals vaccinated with DNA encoding DEC205-targeted antigens. By this, we could exclude the general deletion of antigen-specific T cells as cause for the reduced efficacy, but observed a local expansion of antigen-specific regulatory T cells, which could suppress the activation of effector cells. In conclusion, DNA vaccines encoding DEC205-targeted antigens induce peripheral tolerance rather than immunity in our study. Finally, we evaluated our DNA vaccines as prophylactic or therapeutic treatment in an allergen-induced asthma mouse model. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 145
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 103685890
- Full Text :
- https://doi.org/10.1111/imm.12467