Induction of immune responses by attenuated isogenic mutant strains of Listeria monocytogenes.

We have generated isogenic Listeria monocytogenes mutant strains to study the induction of protective immunity in mice. These strains harbored either a specific deletion within the actin nucleator (actA) and/or have multiple deletions within the actA and phospholipase B (plcB) genes. In comparison to the wild type parental L. monocytogenes EGDe strains, the mutant strains were extremely low in virulence and were rapidly eliminated by the host during the first days of infection. Nevertheless, a single immunization with both mutant strains (EGDe DeltaactA2 and DeltaactADeltaplcB) efficiently induced and maintained effector memory (CD8(+)) T cells and has provided animals with a state of long-lasting protective immunity against wild type L. monocytogenes. These mutant strains can be used as live vaccines against the corresponding virulent pathogen and as carriers for introducing heterologous protective antigens into animals and humans.