Induction of specific CD8+memory T cells and long lasting protection following immunization with Salmonella typhimurium expressing a lymphocytic choriomeningitis MHC class I-restricted epitope

Numerous studies have shown the potential of Salmonella typhimurium as a ve ctor for delivery of heterologous proteins for vaccination against other pa thogens. Earlier studies showed that the inefficient elicitation of MHC cla ss I-restricted responses could limit the use of S. typhimurium as a hetero logous antigen delivery vector for vaccination. We recently developed an ap proach to overcome this limitation by using a bacterial-encoded specialized protein secretion system, termed type III, to deliver proteins into the cl ass I antigen presenting pathways. Thus. peptides of interest fused to prot eins bearing the type III secretion signal, which can elicit protective CTL responses. Because protective immunity is usually assessed a few weeks aft er vaccination, there is a paucity of information regarding duration of pro tective immunity induced by this system. We show here that mice immunized o rally with S. typhimurium vectors expressing a MHC class I-restricted epito pe of the lymphocytic choriomeningitis virus (LCMV) nucleoprotein developed specific antiviral CTL responses. CD8+ T cells were found to be necessary for this CTL activity against targets presenting the LCMV epitope. The surv ival of mice challenged with lethal doses of LCMV 60 or 135 days after vacc ination was as complete as the survival of mice challenged 2 weeks after im munization with the same vectors. By demonstrating their ability to induce prolonged protective immunity after oral delivery, S. typhimurium vectors h ave met an essential requirement in support of their development as vectors for heterologous vaccination. (C) 2001 Elsevier Science Ltd. All rights re served.