Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis.
Lipoarabinomannan (LAM) is a major structural surface component of mycobacteria. Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen. The different AM oligosaccharide (AMOs)-protein conjugate vaccine candidates proved to be highly immunogenic, inducing boosterable IgG responses against the AMOs portion of the conjugates in rabbits and guinea-pigs. Proliferation of T-cells from C57BL/6 mice immunized with the conjugates was seen upon in vitro stimulation with PPD. In C57BL/6 mice subcutaneous immunization with the AMOs-antigen 85B conjugate in alum provided significant protection compared to sham (alum only) immunized mice (P < 0.021) as estimated by long term survival against intravenous challenge with 10(5) M. tuberculosis H37Rv. Subcutaneous immunization followed by nasal boost with an AMOs-TT conjugate in Eurocine L3 adjuvant provided high (P < 0.025) protection as determined by long term survival after intranasal challenge with 10(5) virulent M. tuberculosis strain Harlingen. This level of protection was comparable to that obtained with the conventional live attenuated BCG vaccine. In guinea-pigs, immunization with AMOs-Ag85B in Eurocine L3 adjuvant followed by aerogenic challenge with M. tuberculosis H37Rv resulted in increased survival and reduced pathology in lungs and spleens relative to non-immunized animals.
Hamasur
Beston
B
Swedish Institute for Infectious Disease Control, S-17182 Solna, Sweden.
Haile
Melles
M
Pawlowski
Andrzej
A
Schröder
Ulf
U
Williams
Ann
A
Hatch
Graham
G
Hall
Graham
G
Marsh
Philip
P
Källenius
Gunilla
G
Svenson
Stefan B
SB
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D015169:Colony Count, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D007114:Immunization; D008168:Lung / Q000382:microbiology; D008351:Mannans / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000276:immunology*; D009844:Oligosaccharides / Q000737:chemistry; D011817:Rabbits; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D032581:Tuberculosis Vaccines / Q000737:chemistry / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D018074:Vaccines, Conjugate / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001426:Bacterial Proteins; D008351:Mannans; D009844:Oligosaccharides; D032581:Tuberculosis Vaccines; D018074:Vaccines, Conjugate; C041524:aluminum sulfate; C012189:arabinomannan