The Mycobacterium tuberculosis recombinant 27-kilodalton lipoprotein induces a strong Th1-type immune response deleterious to protection.
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.
Hovav
Avi-Hai
AH
Department of Clinical Microbiology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Mullerad
Jacob
J
Davidovitch
Liuba
L
Fishman
Yolanta
Y
Bigi
Fabiana
F
Cataldi
Angel
A
Bercovier
Herve
H
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008074:Lipoproteins / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D008074:Lipoproteins; D011994:Recombinant Proteins