| Literature DB >> 25657094 |
Peter Sander1, Simon Clark2, Agnese Petrera3, Cristina Vilaplana4, Michael Meuli3, Petra Selchow3, Andrea Zelmer5, Deepa Mohanan6, Nuria Andreu5, Emma Rayner2, Michael Dal Molin3, Gregory J Bancroft5, Pål Johansen6, Pere-Joan Cardona4, Ann Williams2, Erik C Böttger7.
Abstract
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 Δzmp1 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 Δzmp1 for use in clinical trials.Entities:
Keywords: BCG; Guinea pig; Live vaccine; Protease; Protection; Safety; Tuberculosis
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Year: 2015 PMID： 25657094 DOI： 10.1016/j.vaccine.2015.01.058
Source DB: PubMed Journal: Vaccine ISSN： 0264-410X Impact factor: 3.641