title: Phosphatidylinositol di-mannoside and derivates modulate the immune response to and efficacy of a tuberculosis protein vaccine against Mycobacterium bovis infection.
abstract: Mycobacterium bovis infects a wide range of hosts, including domestic livestock, wildlife, and humans. Development of an effective vaccine protecting against bovine tuberculosis would provide a cost-effective tuberculosis control strategy. The objective of this study was to investigate the ability of phosphatidylinositol di-mannoside (PIM(2)) and its derivatives to modulate cell-mediated immunity in vivo in a bovine tuberculosis mouse model in response to a relevant antigen, namely a fusion protein of mycobacterial proteins Ag85A and ESAT-6. The addition of synthetic PIM(2) to the vaccine resulted in a significant reduction in lung bacterial counts and a cytokine profile indicating a Th 1 type immune response. The addition of the other PIM(2) derivatives to the vaccine or the fusion protein alone did not result in reduced lung bacterial counts; moreover, the addition of PIM(2)ME appeared to negate the induction of an antigen-specific interferon-γ response and protection against tuberculosis. In conclusion, this study provides further evidence that PIMs can function as potent adjuvants for protein or sub-unit vaccines, but subtle structural differences among PIMs can markedly alter the type of immune response induced.
authors: AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Tennent Drive, Private Bag 11008, Palmerston North 4442, New Zealand.
authors: Natalie A
authors: NA
authors: Parlane
authors: Benjamin J
authors: BJ
authors: Compton
authors: Colin M
authors: CM
authors: Hayman
authors: Gavin F
authors: GF
authors: Painter
authors: Randall J
authors: RJ
authors: Basaraba
authors: Axel
authors: A
authors: Heiser
authors: Bryce M
authors: BM
authors: Buddle
mesh_terms: D000217:Acyltransferases / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D010716:Phosphatidylinositols / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010716:Phosphatidylinositols; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; C054977:phosphatidylinositol dimannoside; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis