Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination

F. Schodel, S. M. Kelly, D. L. Peterson, D. R. Milich, R. Curtiss

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59 Scopus citations


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 Δcya Δcrp 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 Δcya Δcrp mutant vaccine strains in this balanced, lethal host- vector combination. A single oral immunization of BALB/c mice with a recombinant S. typhimurium Δcya Δcrp 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 Δcya Δcrp strain expressing the same HBcAg-pre-S gene had reduced immunogenicity for the carried antigen after oral immunization.

Original languageEnglish (US)
Pages (from-to)1669-1676
Number of pages8
JournalInfection and Immunity
Issue number5
Publication statusPublished - 1994
Externally publishedYes


ASJC Scopus subject areas

  • Immunology

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