Safe Live Oral Salmonella Vaccines; Use of aro- Strains

摘要

Tests of available reduced-virulence auxotrophic mutants of S. typhi showed the aspartate mutant to be ppc, deficient of phosphoenolpyruvate carboxylase; a PAB mutant to be affected at the locus mutated in S. typhimurium mutants pab-501 and pab-503 and mutant 479 to have an early block in purine biosynthesis, at an unidentified locus. Complete blocks in aromatic or purine biosynthesis, or at ppc, resulting from insertion of transposon Tn10 were transduced into two wild-type S. typhi strains; non-reverting secondary mutations were obtained. Defect at ppc did not much affect virulence, but the aro and pur strains were of greatly reduced virulence (LD50 in mouse, i.p., with hog gastric mucin, increased by 10 to the 4th power - 10 to the 5th power) and an aro pur strain was even less virulent then either single-defect class. Such constructed strains, non-virulent but anitgenically unaltered, may be of use as live, oral-route typhoid vaccines. S typhi strains of low virulence because of pur defects may be of use as 'safe' strains for laboratory teaching; aro strains, because unable to grow on media such as blood agar, are not suitable.