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

Isogenic mutant strains of Listeria monocytogenes demonstrating 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 that L. monocytogenes mutants of reduced virulence have the potential to act as vaccines only if they are sufficiently persistent 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 creating Listeria monocytogenes strains with potential for use as attenuated live vaccines.