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

被引:14
作者
Ashby, D
Leduc, I
Lauzon, W
Lee, BC
Singhal, N
Cameron, DW
机构
[1] Univ Ottawa, Dept Med, Div Infect Dis, Ottawa Hosp, Ottawa, ON K1H 8L6, Canada
[2] Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada
[3] Ottawa Hosp, Clin Epidemiol Program, Ottawa Hlth Res Inst, Ottawa, ON, Canada
关键词
animal model; chancroid vaccine; Haemophilus ducreyi; recombinant antigens; attenuated Salmonella;
D O I
10.1016/j.jim.2005.02.005
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 cliancroid, 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 temperaturedependent rabbit model of H. ducreyi infection, ail in vivo quantitative virulence assay of inducible immunity. We identified 108 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 pTETuir15 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 skill 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. (c) 2005 Elsevier B.V All rights reserved.
引用
收藏
页码:153 / 164
页数:12
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