title: The differential impact of coadministered vaccines, geographic region, vaccine product and other covariates on pneumococcal conjugate vaccine immunogenicity.
abstract: BACKGROUND
  Antipneumococcal capsular polysaccharide antibody concentrations are used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal disease among infants. While pneumococcal conjugate vaccines (PCV) are recommended globally, factors associated with optimal PCV immune response are not well described. We aimed to systematically assess local setting factors, beyond dosing schedule, which may affect PCV antibody levels.
  
  
  METHODS
  We conducted a literature review of PCV immunogenicity, abstracting data from published reports, unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011 reports). Studies included in this analysis evaluated ≥ 2 primary doses of PCV before 6 months of age in non-high-risk populations, used 7-valent or higher PCV products (excluding Aventis-Pasteur and Merck products) and provided information on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using random effects meta-regression, we assessed the impact of geographic region, coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing schedule and ELISA laboratory method.
  
  
  RESULTS
  Of 12,980 citations reviewed, we identified 103 vaccine study arms for this analysis. Children in studies from Asia, Africa and Latin America had significantly higher GMC responses compared with those in studies from Europe and North America. Coadministration with acellular pertussis DTP compared with whole-cell DTP had no effect on PCV immunogenicity except for ST14, where GMCs were higher when coadministered with acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval, age at first dose and ELISA laboratory method also affected the GMC.
  
  
  CONCLUSIONS
  PCV immunogenicity is associated with geographic region and vaccine product; however, the associations and magnitude varied by ST. Consideration of these factors is essential when comparing PCV immunogenicity results between groups and should be included in the evidence base when selecting optimal PCV vaccine schedules in specific settings.
authors: From the *International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; †Biostatistics Consulting, Chicago, IL; ‡Respiratory Diseases Branch, Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; §Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA; and ¶Institute of Child Health, University College London, London, United Kingdom.
authors: Daniel E
authors: DE
authors: Park
authors: T Scott
authors: TS
authors: Johnson
authors: Bareng Aletta S
authors: BA
authors: Nonyane
authors: Subhash
authors: S
authors: Chandir
authors: Laura
authors: L
authors: Conklin
authors: Katherine E
authors: KE
authors: Fleming-Dutra
authors: Jennifer D
authors: JD
authors: Loo
authors: David
authors: D
authors: Goldblatt
authors: Cynthia G
authors: CG
authors: Whitney
authors: Katherine L
authors: KL
authors: O'Brien
authors: Maria
authors: M
authors: Deloria Knoll
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate