Systematic review of the effect of pneumococcal conjugate vaccine dosing schedules on immunogenicity

Maria Deloria Knoll, Daniel E. Park, T. Scott Johnson, Subash Chandir, Bareng Aletta S. Nonyane, Laura Conklin, Katherine E. Fleming-Dutra, Jennifer D. Loo, David Goldblatt, Cynthia G. Whitney, Katherine L. O'Brien

Research output: Contribution to journalReview articlepeer-review

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 threedose 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.

Original languageEnglish (US)
Pages (from-to)S119-S129
JournalPediatric Infectious Disease Journal
Volume33
Issue numberSUPPL. 2
DOIs
StatePublished - 2014

Keywords

  • Immunization schedule
  • Immunogenicity
  • Pneumococcal conjugate vaccine

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

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