Humanized NOG mice as a model for tuberculosis vaccine-induced immunity: a comparative analysis with the mouse and guinea pig models of tuberculosis

Immunology. 2017 Sep;152(1):150-162. doi: 10.1111/imm.12756. Epub 2017 Jun 19.

Abstract

The humanized mouse model has been developed as a model to identify and characterize human immune responses to human pathogens and has been used to better identify vaccine candidates. In the current studies, the humanized mouse was used to determine the ability of a vaccine to affect the immune response to infection with Mycobacterium tuberculosis. Both human CD4+ and CD8+ T cells responded to infection in humanized mice as a result of infection. In humanized mice vaccinated with either BCG or with CpG-C, a liposome-based formulation containing the M. tuberculosis antigen ESAT-6, both CD4 and CD8 T cells secreted cytokines that are known to be required for induction of protective immunity. In comparison to the C57BL/6 mouse model and Hartley guinea pig model of tuberculosis, data obtained from humanized mice complemented the data observed in the former models and provided further evidence that a vaccine can induce a human T-cell response. Humanized mice provide a crucial pre-clinical platform for evaluating human T-cell immune responses in vaccine development against M. tuberculosis.

Keywords: T cell; cytokines; rodent; tuberculosis; vaccination.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / microbiology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Guinea Pigs
  • Humans
  • Leukocyte Common Antigens / blood
  • Leukocyte Common Antigens / immunology
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Lung / microbiology
  • Mesenchymal Stem Cell Transplantation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / metabolism
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / immunology
  • Phenotype
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control*
  • Vaccination

Substances

  • BCG Vaccine
  • CpG ODN 2395
  • Cytokines
  • Oligodeoxyribonucleotides
  • Leukocyte Common Antigens
  • PTPRC protein, human