The LTK63 adjuvant improves protection conferred by Ag85B DNA-protein prime-boosting vaccination against Mycobacterium tuberculosis infection by dampening IFN-γ response

• Published in: Vaccine Vol. 26; no. 33; pp. 4237 - 4243
• Main Authors: Palma, Carla, Iona, Elisabetta, Giannoni, Federico, Pardini, Manuela, Brunori, Lara, Fattorini, Lanfranco, Del Giudice, Giuseppe, Cassone, Antonio
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05-08-2008; Elsevier
• Subjects: Acyltransferases - genetics; Acyltransferases - immunology; Adjuvant; Adjuvants, Immunologic - pharmacology; Allergy and Immunology; Animals; Antibodies, Bacterial - blood; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Applied microbiology; Bacterial Toxins - pharmacology; Bacteriology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Colony Count, Microbial; Enterotoxins - pharmacology; Escherichia coli Proteins - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Immunization, Secondary; Immunoglobulin G - blood; Lung - microbiology; Mice; Microbiology; Miscellaneous; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Th1 responses; Tuberculosis - prevention & control; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, Subunit - genetics; Vaccines, Subunit - immunology; Mycobacterium tuberculosis; Th1 responses; Adjuvant; Cytokine; Th1 lymphocyte; Helper cell; Mycobacterial infection; Genetic vaccine; Adjuvant,Mycobacterium tuberculosis,Th1 responses; Protein; Infection; Mycobacteriales; Immunological adjuvant; T-Lymphocyte; Bacteriosis; Mycobacteriaceae; Bacteria; Actinomycetes; Gamma interferon
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.05.050

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-γ 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-γ response by an adjuvant is a novel finding which could be of relevance in tuberculosis vaccination.