title: Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells.
abstract: Modified vaccinia Ankara-expressing Ag85A (MVA85A) is a new tuberculosis (TB) vaccine aimed at enhancing immunity induced by BCG. We investigated the safety and immunogenicity of MVA85A in healthy adolescents and children from a TB endemic region, who received BCG at birth. Twelve adolescents and 24 children were vaccinated and followed up for 12 or 6 months, respectively. Adverse events were documented and vaccine-induced immune responses assessed by IFN-gamma ELISpot and intracellular cytokine staining. The vaccine was well tolerated and there were no vaccine-related serious adverse events. MVA85A induced potent and durable T-cell responses. Multiple CD4+ T-cell subsets, based on expression of IFN-gamma, TNF-alpha, IL-2, IL-17 and GM-CSF, were induced. Polyfunctional CD4+ T cells co-expressing IFN-gamma, TNF-alpha and IL-2 dominated the response in both age groups. A novel CD4+ cell subset co-expressing these three Th1 cytokines and IL-17 was induced in adolescents, while a novel CD4+ T-cell subset co-expressing Th1 cytokines and GM-CSF was induced in children. Ag-specific CD8+ T cells were not detected. We conclude that in adolescents and children MVA85A safely induces the type of immunity thought to be important in protection against TB. This includes induction of novel Th1-cell populations that have not been previously described in humans.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, and School of Child and Adolescent Health, University of Cape Town, Observatory, South Africa.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Michele
authors.initials: M
authors.lastname: Tameris
authors.forename: Nazma
authors.initials: N
authors.lastname: Mansoor
authors.forename: Erica
authors.initials: E
authors.lastname: Smit
authors.forename: Linda
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Fatima
authors.initials: F
authors.lastname: Isaacs
authors.forename: Alana
authors.initials: A
authors.lastname: Keyser
authors.forename: Sizulu
authors.initials: S
authors.lastname: Moyo
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Brittain
authors.forename: Alison
authors.initials: A
authors.lastname: Lawrie
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gelderbloem
authors.forename: Ashley
authors.initials: A
authors.lastname: Veldsman
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.forename: Anthony
authors.initials: A
authors.lastname: Hawkridge
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000009:adverse effects / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis