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High mobility group box 1 acts as an adjuvant for tuberculosis subunit vaccines
Author(s) -
Grover Ajay,
Troudt Jolynn,
Foster Chad,
Basaraba Randall,
Izzo Angelo
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12236
Subject(s) - esat 6 , hmgb1 , adjuvant , immune system , antigen , fusion protein , immunology , biology , protein subunit , tuberculosis , mycobacterium tuberculosis , medicine , inflammation , recombinant dna , biochemistry , pathology , gene
Summary In order to ensure an ample supply of quality candidate tuberculosis ( TB ) subunit vaccines for clinical trials, it is imperative to develop new immunostimulatory adjuvants. High M obility B ox G roup 1 ( HMGB 1), a member of the alarmin group of immunostimulatory proteins, is released by antigen‐presenting cells under various conditions and has been shown to induce T helper type 1 cytokines. We report that HMGB 1 is effective as an adjuvant to enhance the protective efficacy and cellular immune response of TB subunit vaccines and that it is not dependent on the interaction between HMGB 1 and receptor for advanced glycation end products, a major receptor for HMGB 1. In the mouse model of TB , HMGB 1 protein, when formulated with dioctadecylammonium bromide and 6000 MW early secretory antigenic target ( ESAT ‐6), was protective as a subunit vaccine but did not protect as molecular adjuvant in an ESAT ‐6‐based DNA formulation. We then evaluated the immunoprophylactic and protective potential of a fusion protein of HMGB 1 and ESAT ‐6. The HMGB 1– ESAT ‐6 fusion protein induced strong antigen‐specific T helper type 1 cytokines at 30 days post‐immunization. The fusion protein vaccine enhanced activated and effector memory CD 4 and CD 8 T ‐cell responses in the lungs and spleens of mice at 80 days post vaccination. Vaccination with the HMGB 1– ESAT ‐6 fusion protein also resulted in elevated numbers of poly‐functional CD 4 T cells co‐expressing interleukin‐2, interferon‐ γ and tumour necrosis factor‐ α . The potent cell‐mediated immune response generated by the fusion protein correlated with protection against subsequent challenge with M ycobacterium tuberculosis in the mouse TB model.