title: Immune response induced by a linear DNA vector: influence of dose, formulation and route of injection.
abstract: Previously, minimalistic, immunogenetically defined gene expression (MIDGE) vectors were developed as effective and sophisticated carriers for DNA vaccination. Here we evaluate the influence of dose, formulation and delivery route on the immune response after vaccination with MIDGE-Th1 vectors encoding hepatitis B virus surface antigen (HBsAg). An HBsAg-specific IgG1 and IgG2a antibody response was induced in a dose-dependent manner, whereas the IgG2a/IgG1 ratio was independent of the injected DNA dose. Formulation of MIDGE-HBsAg-Th1 with the cationic pyridinium amphiphile SAINT-18 significantly increased antibody levels of IgG1 and IgG2a compared to the unformulated vector. In contrast, SAINT-18 had neither a significant effect on the IgG2a/IgG1 ratio nor on the type and strength of cellular immunity. Overall, the strongest immune response was generated after intradermal injection, followed by intramuscular and subcutaneous (s.c.) injection. The results show that the formulation of MIDGE-Th1 with SAINT-18 increased the efficacy of the MIDGE-Th1 DNA vaccine and is therefore a suitable approach to improve the efficacy of DNA vaccines also in large animals and humans.
authors.affiliation: MOLOGEN AG, Fabeckstrasse 30, 14195 Berlin, Germany. endmann@mologen.com <endmann@mologen.com>
authors.forename: Anne
authors.initials: A
authors.lastname: Endmann
authors.forename: Michael
authors.initials: M
authors.lastname: Baden
authors.forename: Elena
authors.initials: E
authors.lastname: Weisermann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kapp
authors.forename: Matthias
authors.initials: M
authors.lastname: Schroff
authors.forename: Christiane
authors.initials: C
authors.lastname: Kleuss
authors.forename: Burghardt
authors.initials: B
authors.lastname: Wittig
authors.forename: Christiane
authors.initials: C
authors.lastname: Juhls
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D019444:Vaccines, DNA