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. 1994 May;62(5):1669–1676. doi: 10.1128/iai.62.5.1669-1676.1994

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

F Schödel 1, S M Kelly 1, D L Peterson 1, D R Milich 1, R Curtiss 3rd 1
PMCID: PMC186381  PMID: 8168928

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.

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Selected References

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