title: Systematic review of the effect of pneumococcal conjugate vaccine dosing schedules on immunogenicity.
abstract: BACKGROUND
  Despite the breadth of studies demonstrating benefits of pneumococcal conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing schedule in infants.
  
  
  METHODS
  We conducted a systematic literature review of PCV immunogenicity published from 1994 to 2010 (supplemented post hoc with studies from 2011). Studies included for analysis evaluated ≥2 doses of 7-valent or higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk infants ≤6 months of age. Impact of PCV schedule on geometric mean antibody concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at various time points; the GMC 1 month postdose 3 (for various dosing regimens) for serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects linear regression, adjusted for product, acellular diphtheria-tetanus-pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory method, age at first dose and geographic region.
  
  
  RESULTS
  From 61 studies, we evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a booster dose, 11 "2+1" (2 primary plus booster) and 42 "3+1" schedules. The GMC after the primary series was higher following 3-dose schedules compared with 2-dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs were generally similar regardless of whether 2 or 3 primary doses were given. GMCs were significantly higher for all serotypes when dose 3 was administered in the second year (2+1) compared with ≤6 months of age (3+0).
  
  
  CONCLUSIONS
  While giving the third dose in the second year of life produces a higher antibody response than when given as part of the primary series in the first 6 months, the lower GMC between the 2-dose primary series and booster may result in less disease protection for infants in that interval than those who completed the 3-dose primary series. Theoretical advantages of higher antibodies induced by giving the third dose in the second year of life, such as increased protection against serotype 1 disease, longer duration of protection or more rapid induction of herd effects, need to be evaluated in practice.
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; ¶Institute of Child Health, University College London, London, United Kingdom.
authors: Maria
authors: M
authors: Deloria Knoll
authors: Daniel E
authors: DE
authors: Park
authors: T Scott
authors: TS
authors: Johnson
authors: Subash
authors: S
authors: Chandir
authors: Bareng Aletta S
authors: BA
authors: Nonyane
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
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate