Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection

Hum Vaccin Immunother. 2017 Dec 2;13(12):2967-2976. doi: 10.1080/21645515.2017.1368598.

Abstract

Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMX formulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. BALB/c mice were immunized three times intramuscularly with these vaccine formulations. Injection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b+) in the draining lymph nodes consistent with a chemotactic adjuvant effect. Advax4+CMX and Advax4+ECMX induced the highest levels of IgG1 and IgG2a antibodies against rCMX and rECMX, respectively. Immunized mice challenged with Mycobacterium tuberculosis (Mtb) had increased vaccine-specific Th1 responses in the lungs together with reduced Mtb - associated alveolar damage, although only the Advax4+ECMX vaccine demonstrated significant reduction of lung bacterial load. This study confirmed Advax4+ECMX as a potential TB vaccine candidate, with potential for further optimization and clinical development.

Keywords: ECMX; TB; adjuvant; advax; delta inulin; tuberculosis; vaccine.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage
  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives
  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Bacterial Load
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Inulin / administration & dosage
  • Inulin / analogs & derivatives*
  • Lung / microbiology
  • Lymph Nodes / immunology
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Oligodeoxyribonucleotides / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Th1 Cells / immunology*
  • Treatment Outcome
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • CPG-oligonucleotide
  • Immunoglobulin G
  • Oligodeoxyribonucleotides
  • Recombinant Fusion Proteins
  • Tuberculosis Vaccines
  • Vaccines, Synthetic
  • delta inulin
  • Acetylmuramyl-Alanyl-Isoglutamine
  • murabutide
  • Inulin