Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis

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

doi:10.1016/j.vaccine.2019.11.085

Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis

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

Department of Microbiology

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1416-1423
Number of pages	8
Journal	Vaccine
Volume	38
Issue number	6
DOIs	https://doi.org/10.1016/j.vaccine.2019.11.085
Publication status	Published - 2020 Feb 5

Bibliographical note

Funding 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.

Funding Information:
This work was supported by the European Commission (contracts NEWTBVAC n?241745 and TBVAC2020 n?643381), Centre National de la Recherche Scientifique, Universit? Paul Sabatier, Agence Nationale de la Recherche (ANR-11-EQUIPEX-0003), Fondation pour la Recherche M?dicale (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.

Funding Information:
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.

Publisher Copyright:
© 2019

All Science Journal Classification (ASJC) codes

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2019.11.085

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Levillain, F., Kim, H., Woong Kwon, K., Clark, S., Cia, F., Malaga, W., Lanni, F., Brodin, P., Gicquel, B., Guilhot, C., Bancroft, G. J., Williams, A., Jae Shin, S., Poquet, Y., & Neyrolles, O. (2020). Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis. Vaccine, 38(6), 1416-1423. https://doi.org/10.1016/j.vaccine.2019.11.085

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title = "Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis",

abstract = "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.",

author = "Florence Levillain and Hongmin Kim and {Woong Kwon}, Kee and Simon Clark and Felipe Cia and Wladimir Malaga and Faye Lanni and Priscille Brodin and Brigitte Gicquel and Christophe Guilhot and Bancroft, {Gregory J.} and Ann Williams and {Jae Shin}, Sung and Yannick Poquet and Olivier Neyrolles",

note = "Funding Information: This work was supported by the European Commission (contracts NEWTBVAC n°241745 and TBVAC2020 n°643381 ), Centre National de la Recherche Scientifique , Universit{\'e} Paul Sabatier , Agence Nationale de la Recherche ( ANR-11-EQUIPEX-0003 ), Fondation pour la Recherche M{\'e}dicale (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. Funding Information: This work was supported by the European Commission (contracts NEWTBVAC n?241745 and TBVAC2020 n?643381), Centre National de la Recherche Scientifique, Universit? Paul Sabatier, Agence Nationale de la Recherche (ANR-11-EQUIPEX-0003), Fondation pour la Recherche M?dicale (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. Funding Information: 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. Publisher Copyright: {\textcopyright} 2019",

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month = feb,

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doi = "10.1016/j.vaccine.2019.11.085",

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Levillain, F, Kim, H, Woong Kwon, K, Clark, S, Cia, F, Malaga, W, Lanni, F, Brodin, P, Gicquel, B, Guilhot, C, Bancroft, GJ, Williams, A, Jae Shin, S, Poquet, Y & Neyrolles, O 2020, 'Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis', Vaccine, vol. 38, no. 6, pp. 1416-1423. https://doi.org/10.1016/j.vaccine.2019.11.085

TY - JOUR

T1 - Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis

AU - Levillain, Florence

AU - Kim, Hongmin

AU - Woong Kwon, Kee

AU - Clark, Simon

AU - Cia, Felipe

AU - Malaga, Wladimir

AU - Lanni, Faye

AU - Brodin, Priscille

AU - Gicquel, Brigitte

AU - Guilhot, Christophe

AU - Bancroft, Gregory J.

AU - Williams, Ann

AU - Jae Shin, Sung

AU - Poquet, Yannick

AU - Neyrolles, Olivier

N1 - Funding 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. Funding Information: This work was supported by the European Commission (contracts NEWTBVAC n?241745 and TBVAC2020 n?643381), Centre National de la Recherche Scientifique, Universit? Paul Sabatier, Agence Nationale de la Recherche (ANR-11-EQUIPEX-0003), Fondation pour la Recherche M?dicale (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. Funding Information: 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. Publisher Copyright: © 2019

PY - 2020/2/5

Y1 - 2020/2/5

N2 - 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.

AB - 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.

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Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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