Temperature-sensitive mutants of Pseudomonas aeruginosa: isolation and preliminary immunological evaluation

The immunogenicity of two temperature-sensitive (ts) mutants of Pseudomonas aeruginosa immunotype 1, isolated and characterized for the development of a safe, live vaccine strain, was evaluated in a mouse protection model. One mutant, A/10/25, had a limited "coasting" property (i.e., continued replication for two divisions) at the nonpermissive temperature (36 degrees C), whereas the other mutant, E/9/9, continued replication for five generations after transfer to 36 degrees C. Groups of 3- to 5-week-old ICR mice were immunized intraperitoneally with various doses of the two ts mutants; at various times thereafter, the mice were challenged intraperitoneally with lethal doses of the parental wild type. The more extensive coaster, E/9/9, induced 100% protection at immunizing doses lower than those required for A/10/25 to induce the same protection (1 x 10(8) to 2 x 10(8) and 6 x 10(8) colony-forming units, respectively). Both ts strains induced significant protection for up to 5 weeks after immunization. The results of these studies suggest that the use of P. aeruginosa ts mutants might provide a novel approach to the prevention of P. aeruginosa colonization of patients with cystic fibrosis.