title: Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide-specific antibody response and protective efficacy.
abstract: Immunization with a tetanus-protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1-TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti-PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1-TT responded with proliferation and IFN-gamma secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2-cytokine responses were observed in mice immunized with Pnc1-TT. Impaired IFN-gamma production upon TT-stimulation in vitro was also reflected in reduced IFN-gamma/IL-5 ratio. The IL--5 response correlated with IgG anti-PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier-specific IL-5 production. These results show that immunization with Pnc1-TT induces carrier-specific T cell responses that increase with age and determine the levels of PPS-specific Ab elicited. Whereas a weak and Th2-biased response was observed in neonatal mice, infant mice showed a mixed Th1-Th2 response as observed in adults.
authors.affiliation: Department of Immunology, Landspitali - University Hospital, Hringbraut, 101 Reykjavik, Iceland.
authors.forename: Håvard
authors.initials: H
authors.lastname: Jakobsen
authors.forename: Solveig
authors.initials: S
authors.lastname: Hannesdottir
authors.forename: Stefania P
authors.initials: SP
authors.lastname: Bjarnarson
authors.forename: Dominique
authors.initials: D
authors.lastname: Schulz
authors.forename: Emanuelle
authors.initials: E
authors.lastname: Trannoy
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Ingileif
authors.initials: I
authors.lastname: Jonsdottir
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate