title: Codelivery of a DNA vaccine and a protein vaccine with aluminum phosphate stimulates a potent and multivalent immune response.
abstract: The study explores the possibility of efficiently codelivering DNA vaccines and protein-based vaccines by formulation with aluminum phosphate (AlPO4). When mixed with aluminum adjuvants, plasmid DNA bound tightly onto aluminum hydroxide [Al(OH)3] but not to AlPO4. Different doses of DNA vaccines formulated with AlPO4 [but not Al(OH)3] induced enhanced humoral responses and supported priming of MHC class I restricted cellular immunity. Different proteins mixed with the plasmid DNA vaccine in the AlPO4 formulation did not impair its immunogenicity. Coinjection of two different vaccine-relevant antigens in the same AlPO4 formulation, one as a DNA vaccine and the other as a recombinant protein, elicited polyvalent, humoral, and cellular immune responses to all antigens delivered. The isotype profiles of the induced humoral responses and the cytokine profiles of the specifically primed T cell responses indicated that the combined vaccines supported copriming of Th1- and Th2-biased as well as balanced responses. These findings indicate that the AlPO4 adjuvant, a widely accepted adjuvant in human vaccination practice, can be used to combine protein- and DNA-based vaccination to prime an enhanced and balanced specific immunity.
authors.affiliation: Institute for Medical Microbiology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kwissa
authors.forename: Erik B
authors.initials: EB
authors.lastname: Lindblad
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schirmbeck
authors.forename: Joerg
authors.initials: J
authors.lastname: Reimann
mesh_terms: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood*; D006512:Hepatitis B Core Antigens / Q000097:blood / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D000911:Antibodies, Monoclonal; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D010710:Phosphates; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; C012714:aluminum phosphate