title: Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans.
abstract: Protective immunity against Mycobacterium tuberculosis depends on the generation of a T(H)1-type cellular immune response, characterized by the secretion of interferon-gamma (IFN-gamma) from antigen-specific T cells. The induction of potent cellular immune responses by vaccination in humans has proven difficult. Recombinant viral vectors, especially poxviruses and adenoviruses, are particularly effective at boosting previously primed CD4(+) and CD8(+) T-cell responses against a number of intracellular pathogens in animal studies. In the first phase 1 study of any candidate subunit vaccine against tuberculosis, recombinant modified vaccinia virus Ankara (MVA) expressing antigen 85A (MVA85A) was found to induce high levels of antigen-specific IFN-gamma-secreting T cells when used alone in bacille Calmette-Guerin (BCG)-naive healthy volunteers. In volunteers who had been vaccinated 0.5-38 years previously with BCG, substantially higher levels of antigen-specific IFN-gamma-secreting T cells were induced, and at 24 weeks after vaccination these levels were 5-30 times greater than in vaccinees administered a single BCG vaccination. Boosting vaccinations with MVA85A could offer a practical and efficient strategy for enhancing and prolonging antimycobacterial immunity in tuberculosis-endemic areas.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK. Helen.mcshane@ndm.ox.ac.uk
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Ansar A
authors.initials: AA
authors.lastname: Pathan
authors.forename: Clare R
authors.initials: CR
authors.lastname: Sander
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Keating
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis