title: The LTK63 adjuvant improves protection conferred by Ag85B DNA-protein prime-boosting vaccination against Mycobacterium tuberculosis infection by dampening IFN-gamma response.
abstract: T helper type-1 response is essential to control Mycobacterium tuberculosis (MTB) infection but excessive antigen-mediated inflammation concurs to pathology. In mice challenged with MTB, the protection elicited by an Ag85B-encoding DNA vaccine, was lost when mice were boosted with Ag85B-protein in the absence of adjuvant. This effect was due to the expansion of a set of IFN-gamma secreting-CD4+ T cells highly responsive to Ag85B-protein but which lost the ability to interact with MTB-infected macrophages and control MTB growth. Ag85B-protein co-administration with the adjuvant LTK63 reduced the expansion of Ag85B-protein-responding CD4+ T cells and allowed the survival of those protective Ag85B-specific CD4+ T cells induced by the Ag85B-encoding DNA vaccine. Consequently, the protection against MTB-infection was restored. LTK63 caused also a marked augmentation of Ag85B-specific antibodies, in particular those belonging to the IgG2b isotype. The recovery of protection through a down-modulation of antigen-specific IFN-gamma response by an adjuvant is a novel finding which could be of relevance in tuberculosis vaccination.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy. c.palma@iss.it
authors.forename: Carla
authors.initials: C
authors.lastname: Palma
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iona
authors.forename: Federico
authors.initials: F
authors.lastname: Giannoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardini
authors.forename: Lara
authors.initials: L
authors.lastname: Brunori
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Fattorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Antonio
authors.initials: A
authors.lastname: Cassone
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D005260:Female; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; C027538:heat-labile enterotoxin, E coli; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis