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

Abstract

Recombinant Salmonella strains expressing heterologous antigens can be delivered by oral route triggering the elicitation of efficient antigen-specific humoral, T helper and cytotoxic responses. The potential of attenuated Salmonella spp. to trigger anti-tumor immunity was evaluated for the first time by using beta-galactosidase (beta-gal) as a model tumor-associated antigen (TAA). Beta-gal was expressed in a Salmonella typhimurium aroA vaccine carrier strain either constitutively or under the control of a promoter activated upon infection. Oral immunization with both vaccine prototypes resulted in the elicitation of beta-gal-specific humoral and cell-mediated immunity. Although both strains were able to trigger antigen-specific CTL, responses were more efficient when the expression was controlled by the promoter activated upon infection. The anti-tumor efficacy of the stimulated response was validated by challenging vaccinated animals with an aggressive fibrosarcoma transfected with beta-gal, which operationally acts as a TAA. Both groups of vaccinated mice exhibited a significant reduction in tumor take and growth with respect to animals vaccinated with plasmidless carrier (p < 0.05). However, the overall efficiency was better in the group in which beta-gal was controlled by the in vivo-activated promoter (85% versus 54%; p < 0.05).