title: Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells.
abstract: BACKGROUND
  A 23-valent unconjugated pneumococcal polysaccharide vaccine (23vP), routinely administered at the age of 65, has limited effectiveness, and revaccination induces attenuated antibody responses. It is not known whether pneumococcal polysaccharide-protein conjugated vaccines (PCV), although highly effective in infants, offer any immunological advantages over 23vP in adults.
  
  
  METHODS
  We immunized adults with schedules combining both PCV and 23vP and investigated B-cell responses to establish whether PCV7 (a 7-valent PCV) induced T-dependent responses in adults, to assess the role of memory B cells in 23vP-induced antibody hyporesponsiveness, and to identify the B-cell subtypes involved.
  
  
  RESULTS
  A single dose of PCV7 induced significant increases in serotype-specific memory B-cell populations in peripheral blood indicating a T-dependent response. Conversely, immunization with 23vP resulted in a decrease in memory B-cell frequency. Furthermore, memory B-cell responses to subsequent immunization with PCV7, when given after 23vP, were attenuated. Notably, B1b cells, a subset important in protecting mice against pneumococci, were also depleted following immunization with 23vP in humans.
  
  
  CONCLUSIONS
  This study indicates that PCV7 may have an immunological advantage over 23vP in adults and that 23vP-induced depletion of memory and B1b-cell subsets may provide a basis for antibody hyporesponsiveness and the limited effectiveness of 23vP. Clinical Trials Registration. ISRCTN: 78768849.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Clutterbuck
authors.forename: Rajeka
authors.initials: R
authors.lastname: Lazarus
authors.forename: Ly-Mee
authors.initials: LM
authors.lastname: Yu
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Bowman
authors.forename: Elizabeth A L
authors.initials: EA
authors.lastname: Bateman
authors.forename: Linda
authors.initials: L
authors.lastname: Diggle
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Tim E
authors.initials: TE
authors.lastname: Peto
authors.forename: Peter C
authors.initials: PC
authors.lastname: Beverley
authors.forename: David
authors.initials: D
authors.lastname: Mant
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate