title: Carrier-mediated enhancement of cognate T cell help: the basis for enhanced immunogenicity of meningococcal outer membrane protein polysaccharide conjugate vaccine.
abstract: Haemophilus influenzae type b capsular polysaccharide (PRP) conjugate vaccines, which are thought to induce T cell-dependent antibody production, induce protective responses after a single dose in individuals under 15 months of age. However, multiple doses of these vaccines are required to induce protective antibody responses in infants, with the exception of PRP conjugated to meningococcal outer membrane proteins (OMPC), which does so after a single dose. The basis for this difference is not fully understood, although others have proposed that OMPC and porins, the major protein component of OMPC, act as adjuvants or mitogens. In this report OMPC is shown to enhance CD40 ligand-mediated, T cell-dependent antibody production in mice. This paralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecules on human neonatal and murine B cells and of Th1 cytokines. Neither porins nor lipopolysaccharide fully reproduced the effects of OMPC. These studies indicate that OMPC acts both as carrier and adjuvant, and thereby enhances T cell-dependent antibody responses in human infants.
authors.affiliation: Department of Immunology, University of Washington, Seattle, 98195, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Melgosa
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: P S
authors.initials: PS
authors.lastname: Linsley
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.forename: M
authors.initials: M
authors.lastname: van Meurs
authors.forename: R A
authors.initials: RA
authors.lastname: Flavell
authors.forename: R K
authors.initials: RK
authors.lastname: Ernst
authors.forename: S I
authors.initials: SI
authors.lastname: Miller
authors.forename: C B
authors.initials: CB
authors.lastname: Wilson
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D018073:Haemophilus Vaccines / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D015854:Up-Regulation; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; D001425:Bacterial Outer Membrane Proteins; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D016207:Cytokines; D018073:Haemophilus Vaccines; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D008562:Membrane Glycoproteins; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate