Pneumococcal Conjugate and Plain Polysaccharide Vaccines Have Divergent Effects on Antigen-Specific B Cells

J Infect Dis. 2012 May 1;205(9):1408-16. doi: 10.1093/infdis/jis212. Epub 2012 Mar 29.

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.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / immunology*
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Humans
  • Immunization, Secondary / methods
  • Immunologic Memory*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Middle Aged
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / immunology*
  • Streptococcus pneumoniae / immunology
  • Streptococcus pneumoniae / pathogenicity
  • Vaccines, Conjugate / immunology

Substances

  • 23-valent pneumococcal capsular polysaccharide vaccine
  • Heptavalent Pneumococcal Conjugate Vaccine
  • Pneumococcal Vaccines
  • Vaccines, Conjugate

Associated data

  • ISRCTN/ISRCTN78768849