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 language||English (US)|
|Number of pages||8|
|Journal||Infection and Immunity|
|Publication status||Published - 1994|
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