title: Cationic lipid-formulated DNA vaccine against hepatitis B virus: immunogenicity of MIDGE-Th1 vectors encoding small and large surface antigen in comparison to a licensed protein vaccine.
abstract: Currently marketed vaccines against hepatitis B virus (HBV) based on the small (S) hepatitis B surface antigen (HBsAg) fail to induce a protective immune response in about 10% of vaccinees. DNA vaccination and the inclusion of PreS1 and PreS2 domains of HBsAg have been reported to represent feasible strategies to improve the efficacy of HBV vaccines. Here, we evaluated the immunogenicity of SAINT-18-formulated MIDGE-Th1 vectors encoding the S or the large (L) protein of HBsAg in mice and pigs. In both animal models, vectors encoding the secretion-competent S protein induced stronger humoral responses than vectors encoding the L protein, which was shown to be retained mainly intracellularly despite the presence of a heterologous secretion signal. In pigs, SAINT-18-formulated MIDGE-Th1 vectors encoding the S protein elicited an immune response of the same magnitude as the licensed protein vaccine Engerix-B, with S protein-specific antibody levels significantly higher than those considered protective in humans, and lasting for at least six months after the third immunization. Thus, our results provide not only the proof of concept for the SAINT-18-formulated MIDGE-Th1 vector approach but also confirm that with a cationic-lipid formulation, a DNA vaccine at a relatively low dose can elicit an immune response similar to a human dose of an aluminum hydroxide-adjuvanted protein vaccine in large animals.
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Endmann
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Klünder
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kapp
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Riede
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Oswald
authors.affiliation: Synvolux Therapeutics B.V., Groningen, The Netherlands.
authors.forename: Eduard G
authors.initials: EG
authors.lastname: Talman
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schroff
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kleuss
authors.affiliation: Synvolux Therapeutics B.V., Groningen, The Netherlands; Department of Pathology and Medical Biology, University of Groningen, Groningen, The Netherlands.
authors.forename: Marcel H J
authors.initials: MH
authors.lastname: Ruiters
authors.affiliation: MOLOGEN AG, Berlin, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Juhls
mesh_terms: D000818:Animals; D016466:CHO Cells; D002412:Cations; D003412:Cricetulus; D005260:Female; D005822:Genetic Vectors / Q000737:chemistry*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011726:Pyridinium Compounds / Q000737:chemistry*; D013552:Swine; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: C532953:1-methyl-4-(9-dioleyl)methylpyridinium; D002412:Cations; C075654:Engerix-B; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011726:Pyridinium Compounds; D019444:Vaccines, DNA