In vivo electroporation of a codon-optimized BER opt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge

Tuberculosis (Edinb). 2018 Dec;113:65-75. doi: 10.1016/j.tube.2018.07.003. Epub 2018 Jul 10.

Abstract

DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BERopt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer+ CD8+ T cells in peripheral blood and IFN-γ-secreting CD8+ T cells in splenocytes. Meanwhile, the BERopt vaccine-induced long-lasting T cell immunity protected BALB/c mice from high dose viral challenge using a modified vaccinia virus Tiantan strain expressing mature Ag85B protein (MVTT-m85B) and the virulent M. tb H37Rv aerosol challenge. Since the BERopt DNA vaccine does not induce anti-vector immunity, the strong immunogenicity and protective efficacy of this novel DNA vaccine warrant its future development for M. tb prevention and immunotherapy to alleviate the global TB burden.

Keywords: BCG; BER(opt); DNA vaccine; Mycobacterium tuberculosis; Tuberculosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / administration & dosage*
  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Aerosols
  • Animals
  • Antigens, Bacterial / administration & dosage*
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / administration & dosage*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / microbiology
  • Cells, Cultured
  • Codon
  • Disease Models, Animal
  • Electrochemotherapy / methods*
  • Female
  • Immunization
  • Immunogenicity, Vaccine*
  • Inhalation Exposure
  • Interferon-gamma / immunology
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity*
  • Spleen / immunology
  • Spleen / microbiology
  • Time Factors
  • Tuberculosis Vaccines / administration & dosage*
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control*
  • Vaccines, DNA / administration & dosage
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology

Substances

  • Aerosols
  • Antigens, Bacterial
  • Bacterial Proteins
  • Codon
  • ESAT-6 protein, Mycobacterium tuberculosis
  • IFNG protein, mouse
  • Rv2660c protein, Mycobacterium tuberculosis
  • Tuberculosis Vaccines
  • Vaccines, DNA
  • Interferon-gamma
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis