HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

High mobility group box 1 acts as an adjuvant for tuberculosis subunit vaccines.

Abstract
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 Mobility Box Group 1 (HMGB1), 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 HMGB1 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 HMGB1 and receptor for advanced glycation end products, a major receptor for HMGB1. In the mouse model of TB, HMGB1 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 HMGB1 and ESAT-6. The HMGB1-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 CD4 and CD8 T-cell responses in the lungs and spleens of mice at 80 days post vaccination. Vaccination with the HMGB1-ESAT-6 fusion protein also resulted in elevated numbers of poly-functional CD4 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 Mycobacterium tuberculosis in the mouse TB model.
AuthorsAjay Grover, Jolynn Troudt, Chad Foster, Randall Basaraba, Angelo Izzo
JournalImmunology (Immunology) Vol. 142 Issue 1 Pg. 111-23 (May 2014) ISSN: 1365-2567 [Electronic] England
PMID24350616 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2013 John Wiley & Sons Ltd.
Chemical References
  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • ESAT-6 protein, Mycobacterium tuberculosis
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • Recombinant Fusion Proteins
  • Tuberculosis Vaccines
  • Vaccines, Subunit
Topics
  • Adjuvants, Immunologic (administration & dosage, pharmacology)
  • Animals
  • Antigens, Bacterial (administration & dosage, immunology)
  • Bacterial Proteins (administration & dosage, immunology)
  • CD8-Positive T-Lymphocytes (drug effects, immunology, microbiology)
  • Cell Line
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Female
  • HMGB1 Protein (administration & dosage, immunology, pharmacology)
  • Immunity, Cellular (drug effects)
  • Immunologic Memory (drug effects)
  • Injections, Subcutaneous
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis (immunology)
  • Recombinant Fusion Proteins (immunology)
  • Th1 Cells (drug effects, immunology, microbiology)
  • Time Factors
  • Tuberculosis Vaccines (administration & dosage, immunology)
  • Tuberculosis, Pulmonary (immunology, microbiology, prevention & control)
  • Vaccines, Subunit (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: