Mice vaccinated with a non-virulent, aromatic-dependent mutant of Salmonella choleraesuis die from challenge with its virulent parent but survive challenge with Salmonella typhimurium

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA Received June 6, 1989 Accepted September 24, 1989 Summary . BALB/c mice given a live vaccine of an aro A mutant of Salmonella choleraesuis by intraperitoneal (i.p.) injection were not protected against i.p. challenge with its virulent parental strain but were protected against i.p. challenge with either of two virulent strains of Salmonella typhimurium (O [1],4,[5],12). Vaccination with a live vaccine of S. typhimurium aro A protected against challenge with S. typhimurium but not with S. choleraesuis . Intraperitoneal administration of either aroA strain evoked high levels of serum antibody against the homologous lipopolysacharide (LPS) as determined by an enzyme immunoassay. Sera from vaccinated mice also reacted with heterologous LPS but at dilutions at least seven-fold lower than homologous endpoint titres. The vaccination schedule employed with either live-vaccine strain conferred an equal degree of resistance to challenge with Listeria monocytogenes . After mixed infection of mice with equal numbers of virulent S. typhimurium and S. choleraesuis by the i.p. route, the former was isolated in numbers at least 50 000 times greater than the latter from the liver and spleen between days 1 and 5. When mice were vaccinated i.p. with S. choleraesuis aroA , L. monocytogenes or P. multocida before mixed infection, neither serotype showed more than a slight predominance in the liver and spleen during the same period. Thus, in relative terms, vaccination with S. choleraesuis aroA or inoculation with unrelated bacteria suppressed the growth of virulent S. typhimurium in mice but allowed virulent S. choleraesuis to multiply. These results clearly show that S. choleraesuis 38 1 can multiply to kill immunised BALB/c mice. Present address: Department of Clinical Bacteriology, F72, Karolinska Institute, Huddinge University Hospital, 141 86 Huddinge, Sweden.