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  • Title: The LTK63 adjuvant improves protection conferred by Ag85B DNA-protein prime-boosting vaccination against Mycobacterium tuberculosis infection by dampening IFN-gamma response.
    Author: Palma C, Iona E, Giannoni F, Pardini M, Brunori L, Fattorini L, Del Giudice G, Cassone A.
    Journal: Vaccine; 2008 Aug 05; 26(33):4237-43. PubMed ID: 18584925.
    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.
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