Vaccination route, infectivity and thioglycollate broth administration: effects on live vaccine efficacy of auxotrophic derivatives of Salmonella choleraesuis

An aromatic-dependent, therefore non-virulent, derivative of a mouse-virulent strain of Salmonella choleraesuis previously shown not to be effective as a live vaccine when given intraperitoneally (i.p.) to Itys mice, was administered to BALB/c mice. Two doses given i.p. or by feeding did not protect against i.p. or oral challenge with 50 to 5000 LD50 of the virulent ancestor strain. By contrast two doses given intravenously (i.v.) gave almost complete protection against i.p. or oral challenge with 500 LD50 and some protection against larger doses. The number of live bacteria (cfu) in the liver and spleen 24 h after administration of the live vaccine was less than 1% of the number inoculated i.p., but c. 25% of the number injected i.v. The number of cfu in the gut 24 h after oral vaccine administration was only c 10(-5) of the number fed. Administration of thioglycollate broth i.p. 5 days before i.p. vaccination increased recovery of live vaccine cfu in the liver and spleen and its protective efficacy. In each case the live vaccine did not multiply extensively in vivo. We have previously shown that a purine- and a thymine-requiring derivative of S. choleraesuis were each considerably attenuated but unlike the aro derivative were effective as i.p. live vaccines in mice. Doses of these strains (c. 10(4) cfu) found protective were administered i.p. to BALB/c mice. Each strain multiplied extensively in the liver and spleen to c. 10(7) cfu by day 6. All these results are in agreement with a correlation of protective efficacy of a live vaccine with the persistence of a large number of the vaccine bacteria in the liver and spleen for several days.