Vaccination of mice with attenuated mutants ofListeria monocytogenes: requirement for induction of macrophage la expression

Isogenic mutant strains ofListeria monocytogenesdemonstrating graded attenuation in mice were used to analyse the correlation between bacterial virulence, ability to induce class II MHC (la) molecules in antigen presenting cells and ability to vaccinate against secondary infection. The mutants used differed only in the amino acid sequence of the thiol-activated hemolysin, Listeriolysin O (LLO). The results indicate thatL. monocytogenesmutants of reduced virulence have the potential to act as vaccines only if they are sufficiently persistant to induce la expression in antigen presenting cells. The findings also suggest that specific mutagenesis of virulence factors, including LLO, could provide an approach for creatingListeria monocytogenesstrains with potential for use as attenuated live vaccines.