Identification of a Mycobacterium bovis BCG auxotrophic mutant that protects guinea pigs against M. bovis and Hematogenous spread of Mycobacterium tuberculosis without sensitization to tuberculin

Mark A. Chambers, Ann Williams, Dolores Gavier-Widén, Adam Whelan, Graham Hall, Philip D. Marsh, Barry R. Bloom, William R. Jacobs, R. Glyn Hewinson

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from Mycobacterium bovis and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with M. tuberculosis relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with M. bovis and protection of the spleens of guinea pigs infected with M. tuberculosis in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.

Original languageEnglish (US)
Pages (from-to)7094-7099
Number of pages6
JournalInfection and Immunity
Volume68
Issue number12
DOIs
StatePublished - Dec 1 2000

Fingerprint

Tuberculin
Mycobacterium bovis
Mycobacterium tuberculosis
Bacillus
Guinea Pigs
Tuberculin Test
Vaccines
Skin Tests
Tuberculosis
Spleen
Severe Combined Immunodeficiency
Attenuated Vaccines
Animal Diseases
Insertional Mutagenesis
Pandemics
Leucine
Immunity
Hypersensitivity
Vaccination
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Identification of a Mycobacterium bovis BCG auxotrophic mutant that protects guinea pigs against M. bovis and Hematogenous spread of Mycobacterium tuberculosis without sensitization to tuberculin. / Chambers, Mark A.; Williams, Ann; Gavier-Widén, Dolores; Whelan, Adam; Hall, Graham; Marsh, Philip D.; Bloom, Barry R.; Jacobs, William R.; Hewinson, R. Glyn.

In: Infection and Immunity, Vol. 68, No. 12, 01.12.2000, p. 7094-7099.

Research output: Contribution to journalArticle

Chambers, Mark A. ; Williams, Ann ; Gavier-Widén, Dolores ; Whelan, Adam ; Hall, Graham ; Marsh, Philip D. ; Bloom, Barry R. ; Jacobs, William R. ; Hewinson, R. Glyn. / Identification of a Mycobacterium bovis BCG auxotrophic mutant that protects guinea pigs against M. bovis and Hematogenous spread of Mycobacterium tuberculosis without sensitization to tuberculin. In: Infection and Immunity. 2000 ; Vol. 68, No. 12. pp. 7094-7099.
@article{211b2c57fcb84938ae2c5d4122137ce6,
title = "Identification of a Mycobacterium bovis BCG auxotrophic mutant that protects guinea pigs against M. bovis and Hematogenous spread of Mycobacterium tuberculosis without sensitization to tuberculin",
abstract = "Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Gu{\'e}rin (BCG), which was originally derived from Mycobacterium bovis and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with M. tuberculosis relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with M. bovis and protection of the spleens of guinea pigs infected with M. tuberculosis in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.",
author = "Chambers, {Mark A.} and Ann Williams and Dolores Gavier-Wid{\'e}n and Adam Whelan and Graham Hall and Marsh, {Philip D.} and Bloom, {Barry R.} and Jacobs, {William R.} and Hewinson, {R. Glyn}",
year = "2000",
month = "12",
day = "1",
doi = "10.1128/IAI.68.12.7094-7099.2000",
language = "English (US)",
volume = "68",
pages = "7094--7099",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Identification of a Mycobacterium bovis BCG auxotrophic mutant that protects guinea pigs against M. bovis and Hematogenous spread of Mycobacterium tuberculosis without sensitization to tuberculin

AU - Chambers, Mark A.

AU - Williams, Ann

AU - Gavier-Widén, Dolores

AU - Whelan, Adam

AU - Hall, Graham

AU - Marsh, Philip D.

AU - Bloom, Barry R.

AU - Jacobs, William R.

AU - Hewinson, R. Glyn

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from Mycobacterium bovis and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with M. tuberculosis relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with M. bovis and protection of the spleens of guinea pigs infected with M. tuberculosis in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.

AB - Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from Mycobacterium bovis and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with M. tuberculosis relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with M. bovis and protection of the spleens of guinea pigs infected with M. tuberculosis in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.

UR - http://www.scopus.com/inward/record.url?scp=0034442696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034442696&partnerID=8YFLogxK

U2 - 10.1128/IAI.68.12.7094-7099.2000

DO - 10.1128/IAI.68.12.7094-7099.2000

M3 - Article

C2 - 11083835

AN - SCOPUS:0034442696

VL - 68

SP - 7094

EP - 7099

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 12

ER -