Secretion of different listeriolysin cognates by recombinant attenuated Salmonella typhimurium: superior efficacy of haemolytic over non-haemolytic constructs after oral vaccination

Viable antigen (Ag) delivery systems expressing defined pathogen-derived pr oteins represent powerful candidates for future vaccination strategies. Her e, recombinant (r)Salmonella typhimurium aroA strains secreting listeriolys in (Hly) of Listeria monocytogenes in haemolytic or nonhaemolytic form were constructed to direct these carriers into cytosolic or phagosomal host cel l compartments, respectively. Oral and intravenous (i.v.) vaccination of mi ce with either construct induced transporter associated with antigen proces sing'-dependent: protection against the intracellular bacterial pathogen L, monocytogenes. Comparison of oral immunization with both rSalmonella const ructs revealed superior vaccine efficacy of the haemolytic rS. typhimurium Hlys construct as compared to the nonhaemolytic rSalmonella Hlys(492) strai n. In contrast, efficacy of i.v. vaccination with either rSalmonella strain did not significantly differ. Therefore, rSalmonella strains secreting bio logically active Hly represent valuable delivery systems for heterologous r Ag or DNA which should be exploited for future mucosal vaccination strategi es. (C) 2000 Editions scientifiques et medicales elsevier SAS.