TY - JOUR
T1 - Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants
T2 - A phase I randomized controlled study
AU - on behalf of the PPR02 Study Team
AU - Brooks, W. Abdullah
AU - Chang, Lee Jah
AU - Sheng, Xiaohua
AU - Hopfer, Robert
AU - de Bruyn, Guy
AU - Bologa, Monica
AU - Menezes, Josemund
AU - Kirby, Daniel
AU - Da Costa, Xavier
AU - Neveu, David
AU - Gurunathan, Sanjay
AU - Goswami, Doli
AU - Yeasmin, Sultana
AU - Parvin, Nasrin
AU - Moshtaq Ahmed, Ahmed
AU - Nahar, Kamrun
AU - Rahman, Mohammed Ziaur
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/26
Y1 - 2015/8/26
N2 - 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.
AB - 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.
KW - Infants
KW - Phase I clinical trials
KW - Pneumococcal vaccine
KW - Streptococcus pneumoniae
KW - WHO Universal Trial Number U1111-1117-7316
UR - http://www.scopus.com/inward/record.url?scp=84939564719&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939564719&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2015.06.078
DO - 10.1016/j.vaccine.2015.06.078
M3 - Article
C2 - 26143615
AN - SCOPUS:84939564719
SN - 0264-410X
VL - 33
SP - 4610
EP - 4617
JO - Vaccine
JF - Vaccine
IS - 36
ER -