Auxotrophic Salmonella typhi as live vaccine

Salmonella typhi 541Ty has deletions at aroA and purA, causing requirement for aromatic metabolites (including p-aminobenzoate) and for adenine. None of 36 volunteers who drank 10(8) to 10(10) bacteria of 541Ty or its Vi-negative mutant 543Ty showed any adverse effect; all gave evidence of cellular immune response but only a few had serum titre increases. S. typhimurium experiments (at the Wellcome Research Laboratories and at Stanford) show that adenine requirement may reduce both bacterial survival in mouse tissues and live-vaccine efficacy. S. typhi attenuated only by block(s) in aromatic biosynthesis may be more effective as oral-route live vaccine.