Vaccine efficacy of Salmonella strains expressing glycoprotein 63 with different promoters

Author:

McSorley S J1,Xu D1,Liew F Y1

Affiliation:

1. Department of Immunology, University of Glasgow, United Kingdom.

Abstract

The development of Salmonella vaccine vectors has been hindered by both the requirement for multiple doses to induce immune responses and a lack of plasmid stability. Direct comparisons of different promoter systems with the same antigen are necessary to address these important issues. We have previously described an AroA- AroD- deletion mutant of Salmonella typhimurium (GID101) which expresses the gene encoding the Leishmania major promastigote surface glycoprotein gp63 (GID101). While this construct provided significant protection against L. major challenge to highly susceptible BALB/c mice, this required at least two oral doses. We report here the use of two different inducible promoters, the nirB and osmC promoters, to improve vaccine efficacy. These constructs (termed GID105 and GID106, respectively) expressed gp63 in vitro under inducible conditions and colonized BALB/c mice after oral administration. GID105 demonstrated greater plasmid stability in vitro and in vivo than did either GID106 or GID101, which expresses gp63 constitutively. Spleen and lymph node cells from mice immunized with a single oral dose of GID105 proliferated in vitro in response to L. major and secreted gamma interferon, whereas cells from mice given the other constructs did not. Mice immunized with a single oral dose of GID1O5 or GID106 developed significantly smaller lesions upon challenge with L. major, whereas mice administered GID101 did not. Mice administered GID105 also showed considerable resistance to Leishmania donovani infection. These data provide a direct comparison of promoter systems and demonstrate that the use of inducible promoters such as the nirB promoter allows a considerable improvement over the previous vaccine construct in terms of protection against infection.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3