title: Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.
abstract: Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.
authors.affiliation: Department of Pathology and Molecular Medicine and Division of Infectious Diseases, Center for Gene Therapeutics, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Michael
authors.initials: M
authors.lastname: Santosuosso
authors.forename: Sarah
authors.initials: S
authors.lastname: McCormick
authors.forename: Xizhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Anna
authors.initials: A
authors.lastname: Zganiacz
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000217:Acyltransferases / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis