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.
Bibliographical noteFunding Information:
This work was supported by the University of Zurich (UZH) , the Swiss National Foundation ( SNF 31003A_153349 ), the European Union ( EU-FP7 , NewTBVAC No 241 745) and the Tuberculosis Vaccine Initiative (TBVI). PJ was supported by the Swiss National Foundation ( 31003A_149323 ). We gratefully acknowledge the support from the Biological Investigations Group at PHE, Porton Down and Mr Robert Gilbert and other members of the BSF staff at LSHTM.
© 2015 Elsevier Ltd.
- Guinea pig
- Live vaccine