Attenuated Salmonella typhimurium SL3261 as a vaccine vector for recombinant antigen in rabbits

• Published in: Journal of immunological methods Vol. 299; no. 1; pp. 153 - 164
• Main Authors: Ashby, Deborah, Leduc, Isabelle, Lauzon, Wallace, Craig Lee, B., Singhal, Neera, Cameron, D. William
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-04-2005; Elsevier
• Subjects: Administration, Oral; Animal model; Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Attenuated Salmonella; Bacteriological methods and techniques used in bacteriology; Bacteriology; Biological and medical sciences; Chancroid - prevention & control; Chancroid vaccine; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Vectors; Haemophilus ducreyi; Haemophilus ducreyi - immunology; Male; Microbiology; Molecular immunology; Plasmids - genetics; Rabbits; Recombinant antigens; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Salmonella typhimurium; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Salmonella Vaccines - administration & dosage; Techniques; Tetanus Toxin - genetics; Tetanus Toxin - immunology; Vaccines, Attenuated - administration & dosage; PBS; Animal model; Chancroid vaccine; CFU; HIV; Recombinant antigens; LB; TetC; Attenuated Salmonella; CA; Haemophilus ducreyi; Rabbit; Vaccine; Lagomorpha; Salmonella typhimurium; Immunological method; Infection; Pasteurellaceae; Vertebrata; Mammalia; Chancroid; Bacteriosis; Bacteria; Recombinant protein; Vector; Enterobacteriaceae
• ISSN: 0022-1759; 1872-7905
• DOI: 10.1016/j.jim.2005.02.005

Oral live
Salmonella vaccine vectors expressing recombinant guest antigens help stimulate systemic, mucosal, humoral, and cell-mediated immune responses against
Salmonella and recombinant antigens. It may be possible to use them effectively against
Haemophilus ducreyi, the bacterium that causes chancroid, a sexually transmitted genital ulcer disease. This study aimed to test the feasibility of using oral
Salmonella vaccine vectors for the evaluation of chancroid vaccine candidates in the temperature-dependent rabbit model of
H. ducreyi infection, an in vivo quantitative virulence assay of inducible immunity. We identified 10
8 to 10
9 CFU to be a safe and immunogenic oral dose range of
S. typhimurium SL3261, by monitoring post-administration onset and course of illness and antibody titre by enzyme immunoassay (EIA). We successfully transduced plasmid pTETnir15 into the strain to produce recombinant
S. typhimurium SL3261(pTETnir15), successfully expressed tetanus toxin fragment C (TetC) in it, and elicited serum anti-TetC titres of 1:6400 by EIA, 4 weeks after inoculation. The course of experimentally induced
H. ducreyi skin lesions in rabbits treated with SL3261(pTETnir15) was similar to that in saline-treated controls. We describe a framework that successfully uses
Salmonella as a vector for recombinant control antigen in the rabbit model of
H. ducreyi infection, and is suitable for pre-clinical evaluation of
Salmonella vector-based
H. ducreyi vaccine antigen candidates.