Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates

Michelle H. Larsen; Karolin Biermann; Bing Chen; Tsungda Hsu; Vasan K. Sambandamurthy; Andrew A. Lackner; Pyone Pyone Aye; Peter Didier; Dan Huang; Linyun Shao; Huiyong Wei; Norman L. Letvin; Richard Frothingham; Barton F. Haynes; Zheng W. Chen; William R. Jacobs

doi:10.1016/j.vaccine.2009.05.050

Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates

Michelle H. Larsen, Karolin Biermann, Bing Chen, Tsungda Hsu, Vasan K. Sambandamurthy, Andrew A. Lackner, Pyone Pyone Aye, Peter Didier, Dan Huang, Linyun Shao, Huiyong Wei, Norman L. Letvin, Richard Frothingham, Barton F. Haynes, Zheng W. Chen, William R. Jacobs

Microbiology & Immunology

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

87 Scopus citations

Abstract

Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc²6020 (ΔlysA ΔpanCD) and mc²6030 (ΔRD1 ΔpanCD) in cynomolgus macaques. In murine models, mc²6020 is rapidly cleared while mc²6030 persists. Both mc²6020 and mc²6030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc²6020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc²6030 vaccinates, but survival did not differ among the groups.

Original language	English (US)
Pages (from-to)	4709-4717
Number of pages	9
Journal	Vaccine
Volume	27
Issue number	34
DOIs	https://doi.org/10.1016/j.vaccine.2009.05.050
State	Published - Jul 23 2009

Keywords

BCG
Mycobacteria
Mycobacterium
Non-human primate
Safety
Tuberculosis
Vaccine

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
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.2009.05.050

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Larsen, M. H., Biermann, K., Chen, B., Hsu, T., Sambandamurthy, V. K., Lackner, A. A., Aye, P. P., Didier, P., Huang, D., Shao, L., Wei, H., Letvin, N. L., Frothingham, R., Haynes, B. F., Chen, Z. W., & Jacobs, W. R. (2009). Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates. Vaccine, 27(34), 4709-4717. https://doi.org/10.1016/j.vaccine.2009.05.050

Larsen, MH, Biermann, K, Chen, B, Hsu, T, Sambandamurthy, VK, Lackner, AA, Aye, PP, Didier, P, Huang, D, Shao, L, Wei, H, Letvin, NL, Frothingham, R, Haynes, BF, Chen, ZW & Jacobs, WR 2009, 'Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates', Vaccine, vol. 27, no. 34, pp. 4709-4717. https://doi.org/10.1016/j.vaccine.2009.05.050

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abstract = "Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc26020 (ΔlysA ΔpanCD) and mc26030 (ΔRD1 ΔpanCD) in cynomolgus macaques. In murine models, mc26020 is rapidly cleared while mc26030 persists. Both mc26020 and mc26030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc26020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc26030 vaccinates, but survival did not differ among the groups.",

keywords = "BCG, Mycobacteria, Mycobacterium, Non-human primate, Safety, Tuberculosis, Vaccine",

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note = "Funding Information: This work was supported in part by the NIH P01 grant AI052816, RO1 AI43170, and CFAR and a public health service grant RR00164 (TNPRC).",

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AU - Hsu, Tsungda

AU - Sambandamurthy, Vasan K.

AU - Lackner, Andrew A.

AU - Aye, Pyone Pyone

AU - Didier, Peter

AU - Huang, Dan

AU - Shao, Linyun

AU - Wei, Huiyong

AU - Letvin, Norman L.

AU - Frothingham, Richard

AU - Haynes, Barton F.

AU - Chen, Zheng W.

AU - Jacobs, William R.

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N2 - Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc26020 (ΔlysA ΔpanCD) and mc26030 (ΔRD1 ΔpanCD) in cynomolgus macaques. In murine models, mc26020 is rapidly cleared while mc26030 persists. Both mc26020 and mc26030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc26020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc26030 vaccinates, but survival did not differ among the groups.

AB - Tuberculosis (TB) remains a global health burden for which safe vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc26020 (ΔlysA ΔpanCD) and mc26030 (ΔRD1 ΔpanCD) in cynomolgus macaques. In murine models, mc26020 is rapidly cleared while mc26030 persists. Both mc26020 and mc26030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc26020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc26030 vaccinates, but survival did not differ among the groups.

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Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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