title: Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis.
abstract: Bacillus Calmette-Guerin (BCG) vaccine has failed to control the global tuberculosis (TB) epidemic, and there is a lack of safe and effective mucosal vaccines capable of potent protection against pulmonary TB. A recombinant replication-deficient adenoviral-based vaccine expressing an immunogenic Mycobacterium tuberculosis Ag Ag85A (AdAg85A) was engineered and evaluated for its potential to be used as a respiratory mucosal TB vaccine in a murine model of pulmonary TB. A single intranasal, but not i.m., immunization with AdAg85A provided potent protection against airway Mycobacterium tuberculosis challenge at an improved level over that by cutaneous BCG vaccination. Systemic priming with an Ag85A DNA vaccine and mucosal boosting with AdAg85A conferred a further enhanced immune protection which was remarkably better than BCG vaccination. Such superior protection triggered by AdAg85 mucosal immunization was correlated with much greater retention of Ag-specific T cells, particularly CD4 T cells, in the lung and was shown to be mediated by both CD4 and CD8 T cells. Thus, adenoviral TB vaccine represents a promising novel vaccine platform capable of potent mucosal immune protection against TB. Our study also lends strong evidence that respiratory mucosal vaccination is critically advantageous over systemic routes of vaccination against TB.
authors.affiliation: Department of Pathology and Molecular Medicine and Division of Infectious Diseases, Centre for Gene Therapeutics, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Lisa
authors.initials: L
authors.lastname: Thorson
authors.forename: Richard W
authors.initials: RW
authors.lastname: Stokes
authors.forename: Michael
authors.initials: M
authors.lastname: Santosuosso
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.forename: Anna
authors.initials: A
authors.lastname: Zganiacz
authors.forename: Mary
authors.initials: M
authors.lastname: Hitt
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000217:Acyltransferases / Q000096:biosynthesis / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007111:Immunity, Cellular / Q000235:genetics; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis