title: Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination.
abstract: Avirulent salmonellae expressing foreign genes are attractive for use as oral vaccine carriers. To facilitate the stable expression of heterologous genes without conferring antibiotic resistance, a deletion of the asdA1 gene was introduced into Salmonella typhimurium and S. typhi delta cya delta crp mutant vaccine strains. An asd-complementing plasmid expressing hybrid hepatitis B virus nucleocapsid-pre-S (HBcAg-pre-S) particles was constructed. These hybrid HBcAg-pre-S particle genes were stably expressed in S. typhimurium and S. typhi delta cya delta crp mutant vaccine strains in this balanced, lethal host-vector combination. A single oral immunization of BALB/c mice with a recombinant S. typhimurium delta cya delta crp mutant synthesizing hybrid HBcAg-pre-S elicited potentially virus-neutralizing anti-pre-S serum immunoglobulin G antibodies. In addition, serum immunoglobulin G recognizing S. typhimurium lipopolysaccharide was induced. Distribution in tissue after oral immunization was analyzed in one plasmid-strain combination. The recombinant S. typhimurium colonized the gut-associated lymphoid tissue and the spleen and persisted for over 4 weeks, retaining the HBcAg-pre-S expression plasmid. An isogenic virulence plasmid-cured S. typhimurium delta cya delta crp strain expressing the same HBcAg-pre-S gene had reduced immunogenicity for the carried antigen after oral immunization.
authors.affiliation: Max-Planck-Institut für Biochemie, Martinsried, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schödel
authors.forename: S M
authors.initials: SM
authors.lastname: Kelly
authors.forename: D L
authors.initials: DL
authors.lastname: Peterson
authors.forename: D R
authors.initials: DR
authors.lastname: Milich
authors.forename: R
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D005260:Female; D006510:Hepatitis B Antibodies / Q000032:analysis; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000276:immunology; D012485:Salmonella typhi / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics*
chemical_list: D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; C050806:presurface protein 1, hepatitis B surface antigen