Attenuated Salmonella enteritidis E23 as a vehicle for the rectal delivery of DNA vaccine coding for HIV‐1 polyepitope CTL immunogen

This study is focusing on elucidation of the capacity of attenuated Salmonella enteritidis E23 (cya, crp) to serve as a vehicle for the rectal delivery of the DNA vaccine. Earlier for creation HIV‐1 candidate DNA vaccine we have designed the polyepitope protein TCI (T‐cell immunogen), which comprises over 80 CTL epitopes from subtype A, B and C HIV‐1 proteins. The gene coding for TCI protein was used to construct the eukaryotic expression plasmid pcDNA‐TCI. The attenuated S. enteritidis E23 was transformed by electroporation with recombinant plasmid pcDNA‐TCI and the expression of the TCI gene was determined in vitro and in vivo. BALB/c mice were rectally immunized with S. enteritidis E23/pcDNA‐TCI (10(8) cfu) twice at 4 week interval. Bacteria were not pathogenic for mice and spontaneously eliminated from mice spleen and liver to 60 days post the immunization. Detectable antibodies were generated in 2 weeks after immunization and their level increased after second immunization. The results of INF‐γ ELISpot show that mice immunized with S. enteritidis E23/pcDNA‐TCI elicited HIV‐specific cellular immune response. This study demonstrates that attenuated S. enteritidis E23 is an effective live vector for rectal delivery of the DNA vaccine pcDNA‐TCI to generate humoral and T‐cellular responses against HIV‐1.