Evaluation of a temperature-restricted, mucosal tuberculosis vaccine in guinea pigs

Tuberculosis (Edinb). 2018 Dec:113:179-188. doi: 10.1016/j.tube.2018.10.006. Epub 2018 Oct 19.

Abstract

Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Guérin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.

Keywords: Intranasal; Mycobacterium; TBvac85; Tuberculosis; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / administration & dosage*
  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Administration, Intranasal
  • Aerosols
  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / administration & dosage*
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / administration & dosage*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Disease Models, Animal
  • Female
  • Guinea Pigs
  • Immunity, Mucosal / drug effects*
  • Immunogenicity, Vaccine
  • Immunoglobulin G / blood
  • Lung / drug effects*
  • Lung / immunology
  • Lung / microbiology
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / pathogenicity
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / immunology
  • Nasal Mucosa / microbiology
  • Temperature
  • Time Factors
  • Tuberculosis Vaccines / administration & dosage*
  • Tuberculosis Vaccines / immunology
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / prevention & control*
  • Vaccination
  • Vaccines, DNA / administration & dosage

Substances

  • Aerosols
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Immunoglobulin G
  • Tuberculosis Vaccines
  • Vaccines, DNA
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis