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Clinical and Vaccine Immunology, February 2006, p. 179-186, Vol. 13, No. 2
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.2.179-186.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Recognition of Stage-Specific Mycobacterial Antigens Differentiates between Acute and Latent Infections with Mycobacterium tuberculosis

Abebech Demissie,1,{dagger} Eliane M. S. Leyten,2,{dagger} Markos Abebe,1 Liya Wassie,1 Abraham Aseffa,1 Getahun Abate,1,{ddagger} Helen Fletcher,4,§ Patrick Owiafe,3 Philip C. Hill,3 Roger Brookes,3 Graham Rook,4 Alimuddin Zumla,4 Sandra M. Arend,2 Michel Klein,2 Tom H. M. Ottenhoff,2 Peter Andersen,5 T. Mark Doherty,5* and the VACSEL Study Group

Armauer Hansen Research Institute, Addis Ababa, Ethiopia,1 Department of Immunohematology and Blood Transfusion and Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands,2 Tuberculosis Division, MRC Laboratories, Fajara, The Gambia,3 The Centre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, London, United Kingdom,4 Department of Tuberculosis Immunology, Statens Serum Institute, Copenhagen, Denmark5

Received 19 July 2005/ Returned for modification 26 August 2005/ Accepted 18 November 2005

Mycobacterium tuberculosis is estimated to infect 80 to 100 million people annually, the majority of whom do not develop clinical tuberculosis (TB) but instead maintain the infection in a latent state. These individuals generally become positive in response to a tuberculin skin test and may develop clinical TB at a later date, particularly if their immune systems are compromised. Latently infected individuals are interesting for two reasons. First, they are an important reservoir of M. tuberculosis, which needs to be considered for TB control. Second, if detected prior to recrudescence of the disease, they represent a human population that is making a protective immune response to M. tuberculosis, which is very important for defining correlates of protective immunity. In this study, we show that while responsiveness to early secretory antigenic target 6 is a good marker for M. tuberculosis infection, a strong response to the 16-kDa Rv2031c antigen (HspX or {alpha}-crystallin) is largely restricted to latently infected individuals, offering the possibility of differential immunodiagnosis of, or therapeutic vaccination against, TB.

* Corresponding author. Present address: Department of Infectious Disease Immunology, Statens Serum Institute, Artillerivej 5, 2300 København S, Denmark. Phone: 45 32 68 38 44. Fax: 45 32 68 30 35. E-mail: TMD{at}ssi.dk.

{dagger} A.D. and E.M.S.L. contributed equally to this study.

{ddagger} Present address: Department of Internal Medicine, Saint Louis University Health Science Center, St. Louis, MO 63110.

§ Present address: Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.

Members of the VACSEL Study Group are listed in Acknowledgments.

Clinical and Vaccine Immunology, February 2006, p. 179-186, Vol. 13, No. 2
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.2.179-186.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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