Immune responses dependent on antigen location in recombinant attenuated Salmonella typhimurium vaccines following oral immunization.

The subcellular location of a recombinant antigen in recombinant attenuated Salmonella vaccines may influence immunogenicity dependent on exposure of the recombinant antigen to cells involved in systemic immune responses. It has been shown that a recombinant attenuated Salmonella vaccine secreting the recombinant Streptococcus pneumoniae PspA (rPspA) antigen specified by pYA3494 induced protective anti-rPspA-specific immune responses (Kang et al. (2002) Infect. Immun. 70, 1739-1749). A recombinant plasmid pYA3496 specifying a His(6)-tagged rPspA (His(6)-rPspA) protein (no apparent signal sequence) caused the rPspA antigen to localize to the cytoplasm of Salmonella. Salmonella vaccines carrying pYA3494 or pYA3496 expressed similar amounts of rPspA. After a single oral immunization in BALB/c mice with 10(9) colony-forming units (CFU) of the recombinant Salmonella vaccines carrying pYA3494 or pYA3496, IgG antibody responses were stimulated to both rPspA and Salmonella lipopolysaccharide (LPS) antigens. The anti-rPspA IgG titer induced by Salmonella carrying pYA3494 (1.9 x 10(7)) was 10(4) times higher than induced by Salmonella carrying pYA3496 (<2.4 x 10(3)).