Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis

Peter Sander, Simon Clark, Agnese Petrera, Cristina Vilaplana, Michael Meuli, Petra Selchow, Andrea Zelmer, Deepa Mohanan, Nuria Andreu, Emma Rayner, Michael Dal Molin, Gregory J. Bancroft, Pål Johansen, Pere Joan Cardona, Ann Williams, Erik C. Böttger

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

© 2015 Elsevier Ltd. 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.
Original languageEnglish
Pages (from-to)1353-1359
JournalVaccine
Volume33
Issue number11
DOIs
Publication statusPublished - 10 Mar 2015

Keywords

  • BCG
  • Guinea pig
  • Live vaccine
  • Protease
  • Protection
  • Safety
  • Tuberculosis

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