title: B-cell development and pneumococcal immunity in vertically acquired HIV infection.
abstract: Many children with HIV infection now survive into adulthood. This study explored the impact of vertically acquired HIV in the era of antiretroviral therapy on the development of humoral immunity.
  
  
  
  Natural and vaccine-related immunity to pneumococcus and B-cell phenotype was characterized and compared in three groups of young adults: those with vertically-acquired infection, those with horizontally acquired infection and healthy controls.
  
  
  
  Serotype-specific pneumococcal (Pnc) immunoglobulin M and G concentrations before and up to 1 year post-Pnc polysaccharide (Pneumovax) immunization were determined, and opsonophagocytic activity was analysed. B-cell subpopulations and dynamic markers of B-cell signalling, turnover and susceptibility to apoptosis were evaluated by flow cytometry.
  
  
  
  HIV-infected patients showed impaired natural Pnc immunity and reduced humoral responses to immunization with Pneumovax; this was greatest in those viraemic at time of the study. Early-life viral control before the age of 10 years diminished these changes. Expanded populations of abnormally activated and immature B-cells were seen in both HIV-infected cohorts. Vertically infected patients were particularly vulnerable to reductions in marginal zone and switched memory populations. These aberrations were reduced in patients with early-life viral control.
  
  
  
  In children with HIV, damage to B-cell memory populations and impaired natural and vaccine immunity to pneumococcus is evident in early adult life. Sustained viral control from early childhood may help to limit this effect and optimize humoral immunity in adult life.
authors.affiliation: aInstitute of Child Health, UCL, London bAddenbrookes Hospital, Cambridge cMortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK dUniversity of Regina, Regina, Saskatchewan, Canada ePapworth Hospital NHS Trust, Cambridge, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Eisen
authors.forename: Clare
authors.initials: C
authors.lastname: Hayden
authors.forename: Carmel J
authors.initials: CJ
authors.lastname: Young
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.forename: Eva
authors.initials: E
authors.lastname: Jungmann
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Jacobsen
authors.forename: Hannah
authors.initials: H
authors.lastname: Poulsom
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Klein
authors.forename: Helen E
authors.initials: HE
authors.lastname: Baxendale
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002648:Child; D018562:Disease Transmission, Infectious; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines