Novel recombinant RD2- and RD11-encoded Mycobacterium tuberculosis antigens are potential candidates for diagnosis of tuberculosis infections in BCG-vaccinated individuals

Jiazhen Chen, Xiaodi Su, Ying Zhang, Sen Wang, Linyun Shao, Jing Wu, Feifei Wang, Shu Zhang, Jiuling Wang, Xinhua Weng, Honghai Wang, Wenhong Zhang

Research output: Contribution to journalArticle

Abstract

Proteins encoded by region of deletions (RD) of Mycobacterium tuberculosis are useful in development of vaccines and diagnostic reagents. In the present study, six M. tuberculosis genes from RD2 and RD11, rv1978, nrdf1, mpt64, cfp-21, ppe57 and ppe59, were cloned and overexpressed in Escherichia coli. All six purified recombinant proteins could distinguish tuberculosis (TB) patients and latent TB infected subjects (LTBI), or called subclinical TB infection, from BCG-vaccinated healthy controls by T-cell IFN-γ releasing ELISPOT. ELISPOT of Rv1978, NrdF1, Mpt64, CFP-21, Ppe57 and Ppe59 achieved sensitivities of 59%, 60%, 82%, 48%, 59% and 47% respectively in the detection of active TB and specificities of 94%, 90%, 76%, 93%, 100% and 93% respectively in BCG-vaccinated healthy controls. Combination of Ppe57 or NrdF1 with early secreted antigen target 6 (ESAT-6) or 10-kDa culture filtrate protein (CFP-10) in the IFN-γ releasing ESLIPOT assay could increase the sensitivities in detecting active TB, for ESAT-6 from 82.1% to 85.7% or 92.9% (P = 0.5 or 0.03, respectively) and for CFP-10 from 67.9% to 78.6% or 83.9%, respectively (both P <0.05). The high sensitivities, specificities and promising antigenic combination of NrdF1 and Ppe57 in detection of TB in BCG-vaccinated controls suggest their potential application in TB diagnosis.

Original languageEnglish (US)
Pages (from-to)876-885
Number of pages10
JournalMicrobes and Infection
Volume11
Issue number10-11
DOIs
StatePublished - Sep 2009

Fingerprint

Mycobacterium bovis
Tuberculosis
Infection
Enzyme-Linked Immunospot Assay
Mycobacterium tuberculosis
Latent Tuberculosis
Antigens
Asymptomatic Infections
Recombinant Proteins
Mycobacterium tuberculosis antigens
Proteins
Vaccines
Escherichia coli
T-Lymphocytes
Sensitivity and Specificity
Genes

Keywords

  • ELISPOT
  • Immunodiagnosis
  • Latent TB infection
  • Mycobacterium tuberculosis
  • RD11-encoded antigens
  • RD2-encoded antigens

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Novel recombinant RD2- and RD11-encoded Mycobacterium tuberculosis antigens are potential candidates for diagnosis of tuberculosis infections in BCG-vaccinated individuals. / Chen, Jiazhen; Su, Xiaodi; Zhang, Ying; Wang, Sen; Shao, Linyun; Wu, Jing; Wang, Feifei; Zhang, Shu; Wang, Jiuling; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong.

In: Microbes and Infection, Vol. 11, No. 10-11, 09.2009, p. 876-885.

Research output: Contribution to journalArticle

Chen, Jiazhen ; Su, Xiaodi ; Zhang, Ying ; Wang, Sen ; Shao, Linyun ; Wu, Jing ; Wang, Feifei ; Zhang, Shu ; Wang, Jiuling ; Weng, Xinhua ; Wang, Honghai ; Zhang, Wenhong. / Novel recombinant RD2- and RD11-encoded Mycobacterium tuberculosis antigens are potential candidates for diagnosis of tuberculosis infections in BCG-vaccinated individuals. In: Microbes and Infection. 2009 ; Vol. 11, No. 10-11. pp. 876-885.
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AU - Chen, Jiazhen

AU - Su, Xiaodi

AU - Zhang, Ying

AU - Wang, Sen

AU - Shao, Linyun

AU - Wu, Jing

AU - Wang, Feifei

AU - Zhang, Shu

AU - Wang, Jiuling

AU - Weng, Xinhua

AU - Wang, Honghai

AU - Zhang, Wenhong

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N2 - Proteins encoded by region of deletions (RD) of Mycobacterium tuberculosis are useful in development of vaccines and diagnostic reagents. In the present study, six M. tuberculosis genes from RD2 and RD11, rv1978, nrdf1, mpt64, cfp-21, ppe57 and ppe59, were cloned and overexpressed in Escherichia coli. All six purified recombinant proteins could distinguish tuberculosis (TB) patients and latent TB infected subjects (LTBI), or called subclinical TB infection, from BCG-vaccinated healthy controls by T-cell IFN-γ releasing ELISPOT. ELISPOT of Rv1978, NrdF1, Mpt64, CFP-21, Ppe57 and Ppe59 achieved sensitivities of 59%, 60%, 82%, 48%, 59% and 47% respectively in the detection of active TB and specificities of 94%, 90%, 76%, 93%, 100% and 93% respectively in BCG-vaccinated healthy controls. Combination of Ppe57 or NrdF1 with early secreted antigen target 6 (ESAT-6) or 10-kDa culture filtrate protein (CFP-10) in the IFN-γ releasing ESLIPOT assay could increase the sensitivities in detecting active TB, for ESAT-6 from 82.1% to 85.7% or 92.9% (P = 0.5 or 0.03, respectively) and for CFP-10 from 67.9% to 78.6% or 83.9%, respectively (both P <0.05). The high sensitivities, specificities and promising antigenic combination of NrdF1 and Ppe57 in detection of TB in BCG-vaccinated controls suggest their potential application in TB diagnosis.

AB - Proteins encoded by region of deletions (RD) of Mycobacterium tuberculosis are useful in development of vaccines and diagnostic reagents. In the present study, six M. tuberculosis genes from RD2 and RD11, rv1978, nrdf1, mpt64, cfp-21, ppe57 and ppe59, were cloned and overexpressed in Escherichia coli. All six purified recombinant proteins could distinguish tuberculosis (TB) patients and latent TB infected subjects (LTBI), or called subclinical TB infection, from BCG-vaccinated healthy controls by T-cell IFN-γ releasing ELISPOT. ELISPOT of Rv1978, NrdF1, Mpt64, CFP-21, Ppe57 and Ppe59 achieved sensitivities of 59%, 60%, 82%, 48%, 59% and 47% respectively in the detection of active TB and specificities of 94%, 90%, 76%, 93%, 100% and 93% respectively in BCG-vaccinated healthy controls. Combination of Ppe57 or NrdF1 with early secreted antigen target 6 (ESAT-6) or 10-kDa culture filtrate protein (CFP-10) in the IFN-γ releasing ESLIPOT assay could increase the sensitivities in detecting active TB, for ESAT-6 from 82.1% to 85.7% or 92.9% (P = 0.5 or 0.03, respectively) and for CFP-10 from 67.9% to 78.6% or 83.9%, respectively (both P <0.05). The high sensitivities, specificities and promising antigenic combination of NrdF1 and Ppe57 in detection of TB in BCG-vaccinated controls suggest their potential application in TB diagnosis.

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KW - RD11-encoded antigens

KW - RD2-encoded antigens

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