Mycobacterium tuberculosis ΔRD1 ΔpanCD

A safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis

Vasan K. Sambandamurthy, Steven C. Derrick, Tsungda Hsu, Bing Chen, Michelle H. Larsen, Kripa V. Jalapathy, Mei Chen, John Kim, Steven A. Porcelli, John Chan, Sheldon L. Morris, William R. Jacobs

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

The global epidemic of tuberculosis (TB), fueled by the growing HIV pandemic, warrants the development of a safe and effective vaccine against TB. We report the construction and characterization of an unlinked double deletion mutant of Mycobacterium tuberculosis H37Rv that deletes both the primary attenuating mutation of BCG (ΔRD1) and two genes required for the synthesis of pantothenate (ΔpanCD). The M. tuberculosis ΔRD1 ΔpanCD (mc26030) mutant undergoes limited replication in mice, and yet is both significantly safer than BCG in immunocompromised mice and also safe in guinea pigs. Additionally, the mc26030 strain does not reactivate in a mouse chemo-immunosuppression model. Importantly, long-lived protective immune responses following immunization with the mc26030 strain prolong the survival of wild type mice, and CD4-deficient mice against an aerosol challenge with virulent M. tuberculosis. Given its overall safety and effectiveness, the mc26030 live attenuated strain should be considered as a human vaccine candidate for protecting both healthy and HIV-infected individuals against TB.

Original languageEnglish (US)
Pages (from-to)6309-6320
Number of pages12
JournalVaccine
Volume24
Issue number37-39
DOIs
StatePublished - Sep 11 2006

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Mycobacterium tuberculosis
tuberculosis
Tuberculosis
mutants
mice
Mycobacterium bovis
Tuberculosis Vaccines
HIV
vaccines
immunosuppression
Pandemics
pandemic
aerosols
Aerosols
guinea pigs
Immunosuppression
Immunization
immunization
Guinea Pigs
Vaccines

Keywords

  • Attenuated strains
  • BCG
  • Mycobacterial vaccines
  • Tuberculosis

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Mycobacterium tuberculosis ΔRD1 ΔpanCD : A safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis. / Sambandamurthy, Vasan K.; Derrick, Steven C.; Hsu, Tsungda; Chen, Bing; Larsen, Michelle H.; Jalapathy, Kripa V.; Chen, Mei; Kim, John; Porcelli, Steven A.; Chan, John; Morris, Sheldon L.; Jacobs, William R.

In: Vaccine, Vol. 24, No. 37-39, 11.09.2006, p. 6309-6320.

Research output: Contribution to journalArticle

Sambandamurthy, Vasan K. ; Derrick, Steven C. ; Hsu, Tsungda ; Chen, Bing ; Larsen, Michelle H. ; Jalapathy, Kripa V. ; Chen, Mei ; Kim, John ; Porcelli, Steven A. ; Chan, John ; Morris, Sheldon L. ; Jacobs, William R. / Mycobacterium tuberculosis ΔRD1 ΔpanCD : A safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis. In: Vaccine. 2006 ; Vol. 24, No. 37-39. pp. 6309-6320.
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