Tuberculosis still claims more lives than any other pathogen, and a vaccine better than BCG is urgently needed. One of the challenges for novel TB vaccines is to protect against all Mycobacterium tuberculosis lineages, including the most virulent ones, such as the Beijing lineage. Here we developed a live attenuated M. tuberculosis mutant derived from GC1237, a Beijing strain responsible for tuberculosis outbreaks in the Canary Islands. The mutant strain is inactivated both in the Rv1503c gene, responsible for surface glycolipid synthesis, and in the two-component global regulator PhoPR. This double mutant is as safe as BCG in immunodeficient SCID mice. In immune-competent mice and guinea pigs, the mutant is as protective as BCG against M. tuberculosis strains of common lineage 4 (Euro-American). By contrast, in mice the vaccine is protective against a M. tuberculosis strain of lineage 2 (East-Asian, Beijing), while BCG is not. These results highlight differences in protection efficacy of live attenuated M. tuberculosis-derived vaccine candidates depending on their genetic background, and provide insights for the development of novel live vaccines against TB, especially in East-Asian countries where M. tuberculosis strains of the Beijing family are highly dominant.
Bibliographical noteFunding Information: This work was supported by the European Commission (contracts NEWTBVAC n°241745 and TBVAC2020 n°643381 ), Centre National de la Recherche Scientifique , Université Paul Sabatier , Agence Nationale de la Recherche ( ANR-11-EQUIPEX-0003 ), Fondation pour la Recherche Médicale (contract DEQ2016 0334902 ), Fondation Bettencourt Schueller. The funding bodies did not have a role on the study design, collection, analysis or interpretation of the data or the writing of the manuscript or in the decision to publish the manuscript.
This work was supported by the Department of Health, UK. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.
Open Access: No Open Access licence
Publisher Copyright: © 2019 Published by Elsevier Ltd.
Citation: Florence Levillain, Hongmin Kim, Kee Woong Kwon, Simon Clark, Felipe Cia, Wladimir Malaga, Faye Lanni, Priscille Brodin, Brigitte Gicquel, Christophe Guilhot, Gregory J. Bancroft, Ann Williams, Sung Jae Shin, Yannick Poquet, Olivier Neyrolles,
Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis, Vaccine, Volume 38, Issue 6, 2020, Pages 1416-1423, ISSN 0264-410X.
- Mycobacterium tuberculosis