Moderate immunodeficiency does not increase susceptibility to Salmonella typhimurium aroA live vaccines in mice

Salmonellae carrying appropriate mutations in genes of the aromatic biosynthesis pathway are effective as live vaccines in animals, and they are candidate typhoid vaccines for human use. They are also very effective as carriers of recombinant antigens from other pathogens to the immune system, eliciting circulatory, secretory, and cell-mediated immunity to foreign antigens. Their attenuation is believed to be due to their requirement for the metabolites p-aminobenzoic acid and 2,3-dihydroxybenzoate, which are not available in mammalian tissues. Immunosuppression (e.g., acquired immunodeficiency syndrome) is a major contraindication to the use of live vaccines. If the avirulence of Aro mutants is largely due to their auxotrophy, they should not be markedly more invasive in immunosuppressed animals. We report that wild-type Salmonella typhimurium M525 of intermediate virulence was much more invasive in sublethally irradiated BALB/c mice than in normal BALB/c mice, whereas sublethal irradiation had little if any effect on the invasiveness of an S. typhimurium aorA vaccine strain apart from a delay in its clearance from the reticuloendothelial system. xid mutant CBA/N mice carry an X-linked B-cell functional defect which results in immunoglobulin G3 agammaglobulinemia, and they are known to be more susceptible to salmonellae in late stages of the infection. We found that whereas male (CBA/N x BALB/c)F1 mice (immunodefective) were more susceptible to wild-type S. typhimurium C5 than female littermates (immunocompetent), there was no difference in the response to the S. typhimurium aroA vaccine strain. The results indicate that moderate immunosuppression does not markedly enhance susceptibility to S. typhimurium aroA live vaccines.