title: The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells.
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.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Godwin
authors.initials: G
authors.lastname: Nchinda
authors.forename: Janelle
authors.initials: J
authors.lastname: Kuroiwa
authors.forename: Margarita
authors.initials: M
authors.lastname: Oks
authors.forename: Christine
authors.initials: C
authors.lastname: Trumpfheller
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schlesinger
authors.forename: Olga
authors.initials: O
authors.lastname: Mizenina
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000906:Antibodies; D000941:Antigens; D015683:Gene Products, gag; D019444:Vaccines, DNA