Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants: A phase I randomized controlled study

on behalf of the PPR02 Study Team

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Pneumococcal protein vaccines (PPrVs) may provide improved protection over currently available polysaccharide and conjugated polysaccharide vaccines. Here, we examined the safety and immunogenicity of a trivalent recombinant PPrV containing PcpA, PhtD, and PlyD1. Methods: This was a phase I, single-center, randomized, observer-blind study with safety review between cohorts. Adults (18-50 years; n=. 30) and then toddlers (12-13 months; n=. 30) were randomized 2:1 to receive aluminum-adjuvanted trivalent PPrV (PPrV. +. adj) containing 50. μg per antigen or placebo. Infants (42-49 days; n=. 220) were next randomized to be injected at 6, 10, and 14 weeks of age with 10. μg PPrV. +. adj or placebo (. n=. 60; 2:1); 25. μg PPrV. +. adj, 25. μg unadjuvanted PPrV, or placebo (. n=. 100; 2:2:1); and 50. μg PPrV. +. adj or placebo (. n=. 60; 2:1). Solicited reactions were recorded for 7 days and unsolicited adverse events for 30 days after each vaccination. Concentrations of antibodies to the three vaccine antigens were measured by enzyme-linked immunosorbent assay. Results: Tenderness/pain was the most frequent injection-site reaction. Abnormal crying and irritability (infants), loss of appetite (toddlers), and headache, malaise, and myalgia (adults) were the most frequent systemic reactions. Reactions were mostly mild or moderate, resolved within 3 days, were not adjuvant- or dose-dependent, and were not increased by repeated vaccination. No immediate adverse events, hypersensitivity reactions, or treatment-related serious adverse events were reported. In all PPrV. +. adj cohorts, at least 75% of subjects had a ≥2-fold increase in all three antibody concentrations. In infants, antibody concentrations were higher with PPrV. +. adj than with unadjuvanted PPrV, higher with three than two vaccinations, and similar at the different vaccine doses. Conclusions: The candidate trivalent PPrV was safe and immunogenic in adults, toddlers, and infants. Addition of aluminum adjuvant improved immunogenicity in infants without changing the safety profile.

Original languageEnglish (US)
Pages (from-to)4610-4617
Number of pages8
JournalVaccine
Volume33
Issue number36
DOIs
StatePublished - Aug 26 2015

Keywords

  • Infants
  • Phase I clinical trials
  • Pneumococcal vaccine
  • Streptococcus pneumoniae
  • WHO Universal Trial Number U1111-1117-7316

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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