期刊
VACCINE
卷 33, 期 11, 页码 1353-1359出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2015.01.058
关键词
Tuberculosis; BCG; Protection; Safety; Live vaccine; Protease; Guinea pig
资金
- University of Zurich (UZH)
- Swiss National Foundation (SNF) [31003A_153349]
- European Union (EU-FP7, NewTBVAC) [241 745]
- Tuberculosis Vaccine Initiative (TBVI)
- Swiss National Foundation [31003A_149323]
- Biological Investigations Group at PHE
- Swiss National Science Foundation (SNF) [31003A_153349, 31003A_149323] Funding Source: Swiss National Science Foundation (SNF)
Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG Delta zmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG Delta zmp1 for use in clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.
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