Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent mycobacterium tuberculosis infection

Vaccine. 2019 Jul 26;37(32):4477-4484. doi: 10.1016/j.vaccine.2019.06.078. Epub 2019 Jun 29.

Abstract

The high global burden of tuberculosis (TB) underscores the urgent need for an effective TB vaccine since the only licensed Bacillus Calmette-Guérin (BCG) vaccine is ineffective in preventing adult pulmonary TB and affords no protection against latent TB infection (LTBI). Herein we investigated the potential of Mycobacterium tuberculosis (Mtb) antigen proteins AEC comprised of Ag85b and ESAT6-CFP10 proteins in conjunction with aluminum (Al) and polyriboinosinic-polyribocytidylic acid (poly-IC) as a novel subunit vaccine against TB. The immunogenicity and protection induced by the adjuvanted vaccine were evaluated in two animal models. Mice vaccinated with AEC/Al/poly-IC exhibited significant antigen-specific humoral immune responses and cell-mediated immunity as determined by immunoassay and multicolor flow cytometric assay, and the protective effect of the vaccine was demonstrated in a guinea pig model of latent Mtb infection. Compared to the control group, the mean pathological scores and bacterial loads in lungs and spleens of AEC/Al/poly-IC-immunized guinea pigs were significantly reduced. These data indicate that the AEC/Al/poly-IC is highly immunogenic in mice and can effectively protect guinea pigs against latent Mtb infection; it may represent a promising candidate vaccine for the control of latent TB.

Keywords: Adjuvant; Immunogenicity; Latent tuberculosis infection; Mycobacterium tuberculosis; Protective efficacy; Subunit vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Aluminum / immunology*
  • Animals
  • Antigens, Bacterial / immunology
  • BCG Vaccine / immunology
  • Bacterial Proteins / immunology
  • Female
  • Guinea Pigs
  • Immunity, Cellular / immunology
  • Immunity, Humoral / immunology
  • Immunization / methods
  • Latent Tuberculosis / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / immunology*
  • Peptide Fragments / immunology*
  • Poly I-C / immunology*
  • Recombinant Fusion Proteins / immunology*
  • Spleen / immunology
  • Tuberculosis Vaccines / immunology
  • Tuberculosis, Pulmonary / immunology
  • Vaccination / methods
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Ag85B-ESAT-6 fusion antigen
  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • CFP-10 protein (71-85), Mycobacterium tuberculosis
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Tuberculosis Vaccines
  • Vaccines, Subunit
  • Aluminum
  • Poly I-C