title: Cellular immune responses to Neisseria meningitidis in children.
abstract: There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-gamma), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-gamma ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-gamma ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production.
authors.affiliation: Departments of Paediatrics and Infectious Diseases & Microbiology, Imperial College School of Medicine, St. Mary's Hospital, London W2 1PG, United Kingdom. AJPollard@csi.com
authors.forename: A J
authors.initials: AJ
authors.lastname: Pollard
authors.forename: R
authors.initials: R
authors.lastname: Galassini
authors.forename: E M
authors.initials: EM
authors.lastname: Rouppe van der Voort
authors.forename: M
authors.initials: M
authors.lastname: Hibberd
authors.forename: R
authors.initials: R
authors.lastname: Booy
authors.forename: P
authors.initials: P
authors.lastname: Langford
authors.forename: S
authors.initials: S
authors.lastname: Nadel
authors.forename: C
authors.initials: C
authors.lastname: Ison
authors.forename: J S
authors.initials: JS
authors.lastname: Kroll
authors.forename: J
authors.initials: J
authors.lastname: Poolman
authors.forename: M
authors.initials: M
authors.lastname: Levin
mesh_terms: D000328:Adult; D000367:Age Factors; D001425:Bacterial Outer Membrane Proteins / Q000145:classification / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control; D008589:Meningococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022401:Meningococcal Vaccines; D009345:Neisseria meningitidis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D022401:Meningococcal Vaccines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma