title: Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guérin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara.
abstract: Heterologous prime-boost immunization strategies can evoke powerful T cell immune responses and may be of value in developing an improved tuberculosis vaccine. We show that recombinant modified vaccinia virus Ankara, expressing Mycobacterium tuberculosis Ag 85A (M.85A), strongly boosts bacille Calmette-Guérin (BCG)-induced Ag 85A specific CD4(+) and CD8(+) T cell responses in mice. A comparison of intranasal (i.n.) and parenteral immunization of BCG showed that while both routes elicited comparable T cell responses in the spleen, only i.n. delivery elicited specific T cell responses in the lung lymph nodes, and these responses were further boosted by i.n. delivery of M.85A. Following aerosol challenge with M. tuberculosis, i.n. boosting of BCG with either BCG or M.85A afforded unprecedented levels of protection in both the lungs (2.5 log) and spleens (1.5 log) compared with naive controls. Protection in the lung correlated with the induction of Ag 85A-specific, IFN-gamma-secreting T cells in lung lymph nodes. These findings support further evaluation of mucosally targeted prime-boost vaccination approaches for tuberculosis.
authors.affiliation: Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom. nilu.goonetikkeke@ndm.ox.ac.uk
authors.forename: Nilu P
authors.initials: NP
authors.lastname: Goonetilleke
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hannan
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Anderson
authors.forename: Roger H
authors.initials: RH
authors.lastname: Brookes
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000217:Acyltransferases / Q000008:administration & dosage / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology; D007271:Injections, Intradermal; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009297:Nasal Mucosa / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016056:Immunodominant Epitopes; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis