Salmonella vaccine carrier strains: effective delivery system to trigger anti-tumor immunity by oral route

Recombinant Salmonella strains expressing heterologous antigens can be deli vered by oral route triggering the elicitation of efficient antigen-specifi c humoral, T helper and cytotoxic responses. The potential of attenuated Sa lmonella spp. to trigger anti-tumor immunity was evaluated for the first ti me by using beta-galactosidase (beta-gal) as a model tumor-associated antig en (TAA). beta-gal was expressed in a Salmonella typhimurium aroA vaccine c arrier strain either constitutively or under the control of a promoter acti vated upon infection. Oral immunization with both vaccine prototypes result ed in the elicitation of beta-gal-specific humoral and cell-mediated immuni ty. Although both strains were able to trigger antigen-specific CTL, respon ses were more efficient when the expression was controlled by the promoter activated upon infection. The anti-tumor efficacy of the stimulated respons e was validated by challenging vaccinated animals with an aggressive fibros arcoma transfected with P-gal, which operationally acts as a TAA. Both grou ps of vaccinated mice exhibited a significant reduction in tumor take and g rowth with respect to animals vaccinated with plasmidless carrier (p < 0.05 ). However, the overall efficiency was better in the group in which beta-ga l was controlled by the in vivo-activated promoter (85 % versus 54 %; p < 0 .05).