title: Neonatal mycobacterial specific cytotoxic T-lymphocyte and cytokine profiles in response to distinct BCG vaccination strategies.
abstract: This study evaluated whether different bacillus Calmette-Guérin (BCG) strains, routes of administration, vaccination age and percutaneous tools influenced immune responses to BCG vaccination in infants. Proliferative responses, cytokine production and cell-mediated cytotoxicity obtained in post-vaccinated children were compared to baseline cord bloods and unvaccinated 10-week-old infants. BCG vaccination generally induced strong lymphoproliferative and T helper type 1 (Th1)-type cytokine responses. There was a trend for greater responsiveness following the intradermal route of vaccination, with Japanese-172 strain and with delaying vaccination until 10 weeks. Cord mononuclear cells differentially stimulated the Th2-type cytokines interleukin-5 (IL-5) and IL-10 selectively in response to BCG, as compared to H37Rv or purified protein derivative stimulation. We document for the first time the generation of mycobacterium-specific cytotoxic T lymphocytes in neonates, following BCG vaccination. Cytotoxic activity correlated with the ratio of interferon-gamma to IL-5, aside from a single instance where use of the Biovac tool resulted in a striking dissociation selectively against H37Rv targets. These data have implications for correlates of protective immunity in design of vaccine studies.
authors.affiliation: Department of Paediatrics and Child Health, Groote Schuur Hospital and University of Cape Town, Rondebosch, Cape Town, South Africa. ghussey@rmh.uct.ac.za
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Marcia L V
authors.initials: ML
authors.lastname: Watkins
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Goddard
authors.forename: Sean
authors.initials: S
authors.lastname: Gottschalk
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Hughes
authors.forename: Karen
authors.initials: K
authors.lastname: Iloni
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Kibel
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Ress
mesh_terms: D000367:Age Factors; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn / Q000276:immunology*; D009163:Mycobacterium bovis / Q000145:classification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D001500:BCG Vaccine; D016207:Cytokines