title: Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis.
abstract: 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.
authors.affiliation: Swedish Institute for Infectious Disease Control, S-17182 Solna, Sweden.
authors.forename: Beston
authors.initials: B
authors.lastname: Hamasur
authors.forename: Melles
authors.initials: M
authors.lastname: Haile
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlowski
authors.forename: Ulf
authors.initials: U
authors.lastname: Schröder
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.forename: Graham
authors.initials: G
authors.lastname: Hatch
authors.forename: Graham
authors.initials: G
authors.lastname: Hall
authors.forename: Philip
authors.initials: P
authors.lastname: Marsh
authors.forename: Gunilla
authors.initials: G
authors.lastname: Källenius
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Svenson
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D001426:Bacterial Proteins; D008351:Mannans; D009844:Oligosaccharides; D032581:Tuberculosis Vaccines; D018074:Vaccines, Conjugate; C041524:aluminum sulfate; C012189:arabinomannan