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Infection and Immunity, June 2003, p. 3146-3154, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3146-3154.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Mycobacterium tuberculosis Recombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

Avi-Hai Hovav,1 Jacob Mullerad,1 Liuba Davidovitch,1 Yolanta Fishman,1 Fabiana Bigi,2 Angel Cataldi,2 and Herve Bercovier1*

Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel,1 Instituto de Biotecnología, CICVyA-INTA, Los Reseros y Las Cabañas, 1712 Castelar, Argentina2

Received 17 January 2003/ Returned for modification 21 February 2003/ Accepted 12 March 2003

Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

* Corresponding author. Mailing address: Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, Jerusalem, P.O.B. 12272, Israel. Phone: 972-2-6758256. Fax: 972-2-6784010. E-mail: hb{at}cc.huji.ac.il.

Editor: W. A. Petri, Jr.

Infection and Immunity, June 2003, p. 3146-3154, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3146-3154.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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