A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab') fragment prolong survival of mice infected with Mycobacterium tuberculosis

Lipoarabinomannan (LAM) is a major structural carbohydrate antigen of the outer surface of Mycobacterium tuberculosis. High antibody titres against LAM are often seen in active tuberculosis (TB). The role of such LAM-specific antibodies in the immune response against TB is unknown. Here we have inve...

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Bibliographic Details
Published in:Clinical and experimental immunology 2004-10, Vol.138 (1), p.30-38
Main Authors: Hamasur, B, Haile, M, Pawlowski, A, Schroder, U, Kallenius, G, Svenson, S B
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antigens, Bacterial - immunology
Antigens, Surface - immunology
Body Weight - immunology
Dose-Response Relationship, Immunologic
Female
Immunoglobulin Fab Fragments - immunology
Lipopolysaccharides - immunology
Lung - immunology
Medicin och hälsovetenskap
Mice
Mice, Inbred BALB C
Mycobacterium tuberculosis - immunology
Spleen - immunology
Tuberculosis - immunology
Tuberculosis - mortality
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Summary:Lipoarabinomannan (LAM) is a major structural carbohydrate antigen of the outer surface of Mycobacterium tuberculosis. High antibody titres against LAM are often seen in active tuberculosis (TB). The role of such LAM-specific antibodies in the immune response against TB is unknown. Here we have investigated a monoclonal antibody (MoAb) SMITB14 of IgG1 subclass and its corresponding F(ab')(2) fragment directed against LAM from M. tuberculosis strain H37Rv. MoAb SMITB14 was shown by immunofluorescence to bind to whole cells of the clinical isolate M. tuberculosis strain Harlingen as well as to M. tuberculosis H37Rv. The binding of MoAb SMITB14 to LAM was inhibited by arabinomannan (AM) and oligosaccharides (5.2 kDa) derived from LAM, showing that the MoAb binds specifically to the AM carbohydrate portion of LAM. In passive protection experiments BALB/c mice were infected intravenously with M. tuberculosis Harlingen. MoAb SMITB14 was added intravenously either prior to, or together with, the bacteria. The antibody proved to be protective against the M. tuberculosis infection in terms of a dose-dependent reduction in bacterial load in spleens and lungs, reduced weight loss and, most importantly, increased long-term survival.
ISSN:0009-9104
DOI:10.1111/j.1365-2249.2004.02593.x