Immunization of mice with Salmonella typhimurium C5 aroA expressing a genetically toxoided derivative of the pneumococcal toxin pneumolysin.

An attenuated Salmonella strain expressing a genetically toxoided derivative of the pneumococcal toxin pneumolysin was constructed by first transforming a methylation-positive, restriction-negative Salmonella with plasmid pJCP20M, a derivative of pBR322 containing the modified pneumolysin gene. Plasmid DNA was then extracted and transformed into Salmonella typhimurium C5 aroA. The transformant (denoted JM8) was capable of constitutively expressing the modified pneumolysin gene in vitro and stably maintained the recombinant plasmid containing the pneumococcal DNA, even in the absence of antibiotic selection. When JM8, or the parental Salmonella C5 aroA carrying pBR322 (denoted JM6), were administered orally to mice, both strains were capable of at least transient colonization of the Peyer's patches. Sera from JM8 mice (but not those fed JM6) had significant anti-pneumolysin IgG and IgA ELISA titres. Intraperitoneal administration of JM8 resulted in higher anti-pneumolysin IgG titres, but lower specific IgA levels.