Premium
DNA vaccines encoding DEC 205‐targeted antigens: immunity or tolerance?
Author(s) -
Niezold Thomas,
Storcksdieck genannt Bonsmann Michael,
Maaske André,
Temchura Vladimir,
Heinecke Vanessa,
Hannaman Drew,
Buer Jan,
Ehrhardt Christina,
Hansen Wiebke,
Überla Klaus,
Tenbusch Matthias
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12467
Subject(s) - antigen , dna vaccination , biology , immunogenicity , immunology , immune system , virology , adjuvant , immunity , immunization
Summary Targeting of antigens to the endocytic uptake receptor DEC 205 resulted in enhanced antigen presentation by dendritic cells ( DC s). In combination with adjuvants for DC maturation, proteins coupled to an antibody against DEC 205 induced strong pathogen‐specific immune responses, whereas without additional adjuvant tolerance could be induced. As less is known about DNA vaccines encoding DEC 205‐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 DEC 205 enhanced antigen presentation on MHC class II and activation of T ‐cell receptor‐transgenic CD 4 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 DEC 205‐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 DEC 205‐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.