title: Age at Mycobacterium bovis BCG Priming Has Limited Impact on Anti-Tuberculosis Immunity Boosted by Respiratory Mucosal AdHu5Ag85A Immunization in a Murine Model.
abstract: Tuberculosis (TB) remains a global pandemic despite the use of Bacillus Calmette-Guérin (BCG) vaccine, partly because BCG fails to effectively control adult pulmonary TB. The introduction of novel boost vaccines such as the human Adenovirus 5-vectored AdHu5Ag85A could improve and prolong the protective immunity of BCG immunization. Age at which BCG immunization is implemented varies greatly worldwide, and research is ongoing to discover the optimal stage during childhood to administer the vaccine, as well as when to boost the immune response with potential novel vaccines. Using a murine model of subcutaneous BCG immunization followed by intranasal AdHu5Ag85A boosting, we investigated the impact of age at BCG immunization on protective efficacy of BCG prime and AdHu5Ag85A boost immunization-mediated protection. Our results showed that age at parenteral BCG priming has limited impact on the efficacy of BCG prime-AdHu5Ag85A respiratory mucosal boost immunization-enhanced protection. However, when BCG immunization was delayed until the maturity of the immune system, longer sustained memory T cells were generated and resulted in enhanced boosting effect on T cells of AdHu5Ag85A respiratory mucosal immunization. Our findings hold implications for the design of new TB immunization protocols for humans.
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Daniela
authors.initials: D
authors.lastname: Damjanovic
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Amandeep
authors.initials: A
authors.lastname: Khera
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Afkhami
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rocky
authors.initials: R
authors.lastname: Lai
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Zganiacz
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Mangalakumari
authors.initials: M
authors.lastname: Jeyanathan
authors.affiliation: McMaster Immunology Research Centre and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
mesh_terms: D000367:Age Factors; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine; D032581:Tuberculosis Vaccines