Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial

Vaccine. 2017 May 31;35(24):3256-3263. doi: 10.1016/j.vaccine.2017.04.049. Epub 2017 May 4.


Background: This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS).

Methods: Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35μg/mL (primary endpoint) was greater than -10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected.

Results: 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups.

Conclusions: PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. NCT01964716

Keywords: 2-Phenoxyethanol; Immunogenicity; Multidose vials; Pneumococcal conjugate vaccine; Safety.

Publication types

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

MeSH terms

  • Antibodies, Bacterial / blood
  • Dose-Response Relationship, Immunologic
  • Double-Blind Method
  • Drug Compounding
  • Ethylene Glycols / administration & dosage
  • Ethylene Glycols / chemistry
  • Ethylene Glycols / immunology*
  • Female
  • Gambia / epidemiology
  • Humans
  • Immunization Programs
  • Immunogenicity, Vaccine*
  • Immunoglobulin G / blood
  • Infant
  • Male
  • Pneumococcal Infections / epidemiology
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / adverse effects*
  • Pneumococcal Vaccines / chemistry
  • Pneumococcal Vaccines / immunology*
  • Streptococcus pneumoniae / immunology
  • Vaccination / methods


  • 13-valent pneumococcal vaccine
  • Antibodies, Bacterial
  • Ethylene Glycols
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • phenoxyethanol

Associated data