Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate

Rogelio Hernandez-Pando; Sung Jae Shin; Simon Clark; Stefano Casonato; Martin Becerril-Zambrano; Hongmin Kim; Francesca Boldrin; Dulce Mata-Espinoza; Roberta Provvedi; Ainhoa Arbues; Brenda Marquina-Castillo; Laura Cioetto Mazzabò; Jorge Barrios-Payan; Carlos Martin; Sang Nae Cho; Ann Williams; Riccardo Manganelli

doi:10.1128/IAI.00496-19

Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate

Rogelio Hernandez-Pando, Sung Jae Shin, Simon Clark, Stefano Casonato, Martin Becerril-Zambrano, Hongmin Kim, Francesca Boldrin, Dulce Mata-Espinoza, Roberta Provvedi, Ainhoa Arbues, Brenda Marquina-Castillo, Laura Cioetto Mazzabò, Jorge Barrios-Payan, Carlos Martin, Sang Nae Cho, Ann Williams, Riccardo Manganelli^*

^*Corresponding author for this work

Research & Development Institute Scientific Leaders

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

8 Citations (Scopus)

Abstract

Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health. The only available vaccine (Mycobacterium bovis BCG) protects children from disseminated forms of TB but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against the pulmonary forms of TB a major goal for the improvement of global health. Among the different strategies being developed to reach this goal is the construction of attenuated strains more efficacious and safer than BCG. We recently showed that a sigE mutant of M. tuberculosis was more attenuated and more efficacious than BCG in a mouse model of infection. In this paper, we describe the construction and characterization of an M. tuberculosis sigE fadD26 unmarked double mutant fulfilling the criteria of the Geneva Consensus for entering human clinical trials. The data presented suggest that this mutant is even more attenuated and slightly more efficacious than the previous sigE mutant in different mouse models of infection and is equivalent to BCG in a Guinea pig model of infection.

Original language	English
Article number	e00496-19
Journal	Infection and Immunity
Volume	88
Issue number	1
DOIs	https://doi.org/10.1128/IAI.00496-19
Publication status	Published - 17 Dec 2019

Bibliographical note

Funding Information: This work was supported by the European Community Seventh Framework Program (FP7/2007-2013) under grant agreement 241745 and by the Science and Technology Institute of Mexico City (grant agreement PICSA12-173). Experiments performed in the United Kingdom were supported by the Department of Health, United Kingdom. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

Open Access: Free to read but no Open Access licence.

Publisher Copyright: © 2019 American Society for Microbiology.

Citation: Hernandez-Pando R, Shin SJ, Clark S, Casonato S, Becerril-Zambrano M, Kim H, Boldrin F, Mata-Espinoza D, Provvedi R, Arbues A, Marquina-Castillo B, Cioetto Mazzabò L, Barrios-Payan J, Martin C, Cho S-N, Williams A, Manganelli R. 2020. Construction and characterization of the Mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate. Infect Immun 88:e00496-19.

DOI: https://doi.org/10.1128/IAI.00496-19.

Keywords

BCG
SigE
Sigma factor
Tuberculosis
Vaccine

UN SDGs

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

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10.1128/IAI.00496-19

Cite this

Hernandez-Pando, R., Shin, S. J., Clark, S., Casonato, S., Becerril-Zambrano, M., Kim, H., Boldrin, F., Mata-Espinoza, D., Provvedi, R., Arbues, A., Marquina-Castillo, B., Mazzabò, L. C., Barrios-Payan, J., Martin, C., Cho, S. N., Williams, A., & Manganelli, R. (2019). Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate. Infection and Immunity, 88(1), Article e00496-19. https://doi.org/10.1128/IAI.00496-19

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abstract = "Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health. The only available vaccine (Mycobacterium bovis BCG) protects children from disseminated forms of TB but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against the pulmonary forms of TB a major goal for the improvement of global health. Among the different strategies being developed to reach this goal is the construction of attenuated strains more efficacious and safer than BCG. We recently showed that a sigE mutant of M. tuberculosis was more attenuated and more efficacious than BCG in a mouse model of infection. In this paper, we describe the construction and characterization of an M. tuberculosis sigE fadD26 unmarked double mutant fulfilling the criteria of the Geneva Consensus for entering human clinical trials. The data presented suggest that this mutant is even more attenuated and slightly more efficacious than the previous sigE mutant in different mouse models of infection and is equivalent to BCG in a Guinea pig model of infection.",

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author = "Rogelio Hernandez-Pando and Shin, {Sung Jae} and Simon Clark and Stefano Casonato and Martin Becerril-Zambrano and Hongmin Kim and Francesca Boldrin and Dulce Mata-Espinoza and Roberta Provvedi and Ainhoa Arbues and Brenda Marquina-Castillo and Mazzab{\`o}, {Laura Cioetto} and Jorge Barrios-Payan and Carlos Martin and Cho, {Sang Nae} and Ann Williams and Riccardo Manganelli",

note = "Funding Information: This work was supported by the European Community Seventh Framework Program (FP7/2007-2013) under grant agreement 241745 and by the Science and Technology Institute of Mexico City (grant agreement PICSA12-173). Experiments performed in the United Kingdom were supported by the Department of Health, United Kingdom. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. Open Access: Free to read but no Open Access licence. Publisher Copyright: {\textcopyright} 2019 American Society for Microbiology. Citation: Hernandez-Pando R, Shin SJ, Clark S, Casonato S, Becerril-Zambrano M, Kim H, Boldrin F, Mata-Espinoza D, Provvedi R, Arbues A, Marquina-Castillo B, Cioetto Mazzab{\`o} L, Barrios-Payan J, Martin C, Cho S-N, Williams A, Manganelli R. 2020. Construction and characterization of the Mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate. Infect Immun 88:e00496-19. DOI: https://doi.org/10.1128/IAI.00496-19.",

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Hernandez-Pando, R, Shin, SJ, Clark, S, Casonato, S, Becerril-Zambrano, M, Kim, H, Boldrin, F, Mata-Espinoza, D, Provvedi, R, Arbues, A, Marquina-Castillo, B, Mazzabò, LC, Barrios-Payan, J, Martin, C, Cho, SN, Williams, A & Manganelli, R 2019, 'Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate', Infection and Immunity, vol. 88, no. 1, e00496-19. https://doi.org/10.1128/IAI.00496-19

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T1 - Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate

AU - Hernandez-Pando, Rogelio

AU - Shin, Sung Jae

AU - Clark, Simon

AU - Casonato, Stefano

AU - Becerril-Zambrano, Martin

AU - Kim, Hongmin

AU - Boldrin, Francesca

AU - Mata-Espinoza, Dulce

AU - Provvedi, Roberta

AU - Arbues, Ainhoa

AU - Marquina-Castillo, Brenda

AU - Mazzabò, Laura Cioetto

AU - Barrios-Payan, Jorge

AU - Martin, Carlos

AU - Cho, Sang Nae

AU - Williams, Ann

AU - Manganelli, Riccardo

N1 - Funding Information: This work was supported by the European Community Seventh Framework Program (FP7/2007-2013) under grant agreement 241745 and by the Science and Technology Institute of Mexico City (grant agreement PICSA12-173). Experiments performed in the United Kingdom were supported by the Department of Health, United Kingdom. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. Open Access: Free to read but no Open Access licence. Publisher Copyright: © 2019 American Society for Microbiology. Citation: Hernandez-Pando R, Shin SJ, Clark S, Casonato S, Becerril-Zambrano M, Kim H, Boldrin F, Mata-Espinoza D, Provvedi R, Arbues A, Marquina-Castillo B, Cioetto Mazzabò L, Barrios-Payan J, Martin C, Cho S-N, Williams A, Manganelli R. 2020. Construction and characterization of the Mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate. Infect Immun 88:e00496-19. DOI: https://doi.org/10.1128/IAI.00496-19.

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N2 - Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health. The only available vaccine (Mycobacterium bovis BCG) protects children from disseminated forms of TB but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against the pulmonary forms of TB a major goal for the improvement of global health. Among the different strategies being developed to reach this goal is the construction of attenuated strains more efficacious and safer than BCG. We recently showed that a sigE mutant of M. tuberculosis was more attenuated and more efficacious than BCG in a mouse model of infection. In this paper, we describe the construction and characterization of an M. tuberculosis sigE fadD26 unmarked double mutant fulfilling the criteria of the Geneva Consensus for entering human clinical trials. The data presented suggest that this mutant is even more attenuated and slightly more efficacious than the previous sigE mutant in different mouse models of infection and is equivalent to BCG in a Guinea pig model of infection.

AB - Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health. The only available vaccine (Mycobacterium bovis BCG) protects children from disseminated forms of TB but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against the pulmonary forms of TB a major goal for the improvement of global health. Among the different strategies being developed to reach this goal is the construction of attenuated strains more efficacious and safer than BCG. We recently showed that a sigE mutant of M. tuberculosis was more attenuated and more efficacious than BCG in a mouse model of infection. In this paper, we describe the construction and characterization of an M. tuberculosis sigE fadD26 unmarked double mutant fulfilling the criteria of the Geneva Consensus for entering human clinical trials. The data presented suggest that this mutant is even more attenuated and slightly more efficacious than the previous sigE mutant in different mouse models of infection and is equivalent to BCG in a Guinea pig model of infection.

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Construction and characterization of the mycobacterium tuberculosis sigE fadD26 unmarked double mutant as a vaccine candidate

Abstract

Bibliographical note

Keywords

UN SDGs

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