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The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells

Authors
 Godwin Nchinda  ;  Janelle Kuroiwa  ;  Margarita Oks  ;  Christine Trumpfheller  ;  Chae Gyu Park  ;  Yaoxing Huang  ;  Drew Hannaman  ;  Sarah J. Schlesinger  ;  Olga Mizenina  ;  Michel C. Nussenzweig  ;  Klaus Überla  ;  Ralph M. Steinman 
Citation
 JOURNAL OF CLINICAL INVESTIGATION, Vol.118(4) : 1427-1436, 2008 
Journal Title
 JOURNAL OF CLINICAL INVESTIGATION 
ISSN
 0021-9738 
Issue Date
2008
MeSH
Animals ; Antibodies/immunology ; Antigens/genetics ; Antigens/immunology* ; Antigens/metabolism* ; Cell Line ; Cricetinae ; Dendritic Cells/immunology* ; Gene Products, gag/genetics ; Gene Products, gag/immunology ; Gene Products, gag/metabolism ; Humans ; Mice ; Mucous Membrane/immunology ; T-Lymphocytes/immunology ; Vaccines, DNA/immunology*
Keywords
Animals ; Antibodies/immunology ; Antigens/genetics ; Antigens/immunology* ; Antigens/metabolism* ; Cell Line ; Cricetinae ; Dendritic Cells/immunology* ; Gene Products, gag/genetics ; Gene Products, gag/immunology ; Gene Products, gag/metabolism ; Humans ; Mice ; Mucous Membrane/immunology ; T-Lymphocytes/immunology ; Vaccines, DNA/immunology*
Abstract
DNA vaccines promote an immune response by providing antigen-encoding DNA to the recipient, but the efficacy of such vaccines needs improving. Many approaches have considerable potential but currently induce relatively weak immune responses despite multiple high doses of DNA vaccine. Here, we asked whether targeting vaccine antigens to DCs would increase the immunity and protection that result from DNA vaccines. To determine this, we generated a DNA vaccine encoding a fusion protein comprised of the vaccine antigen and a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Following vaccination of mice, the vaccine antigen was expressed selectively by DCs, which were required for the increased efficacy of MHC class I and MHC class II antigen presentation relative to a control scFv DNA vaccine. In addition, a DNA vaccine encoding an HIV gag p41-scFv DEC205 fusion protein induced 10-fold higher antibody levels and increased numbers of IFN-gamma-producing CD4+ and CD8+ T cells. After a single i.m. injection of the DNA vaccine encoding an HIV gag p41-scFv DEC205 fusion protein, mice were protected from an airway challenge with a recombinant vaccinia virus expressing the HIV gag p41, even with 1% of the dose of nontargeted DNA vaccine. The efficacy of DNA vaccines therefore may be enhanced by inclusion of sequences such as single-chain antibodies to target the antigen to DCs.
Files in This Item:
T200895794.pdf Download
DOI
10.1172/JCI34224
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108678
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