Aderonke Odutola1, Martin O C Ota2, Martin Antonio3, Ezra O Ogundare4, Yauba Saidu5, Patrick K Owiafe6, Archibald Worwui7, Olubukola T Idoko8, Olumuyiwa Owolabi9, Beate Kampmann10, Brian M Greenwood11, Mark Alderson12, Magali Traskine13, Kristien Swinnen14, Vincent Verlant15, Kurt Dobbelaere16, Dorota Borys17. 1. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: aderonke.odutola@lshtm.ac.uk. 2. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: martin.x.ota@gsk.com. 3. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: mantonio@mrc.gm. 4. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: tundeyogundare@yahoo.com. 5. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: ysaidu@clintonhealthaccess.org. 6. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: pkowiafe@uhas.edu.gh. 7. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: aworwui@mrc.gm. 8. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: oidoko@mrc.gm. 9. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia. Electronic address: oowolabi@mrc.gm. 10. Vaccines & Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: bkampmann@mrc.gm. 11. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: Brian.Greenwood@lshtm.ac.uk. 12. PATH, Seattle, WA, USA. Electronic address: malderson@path.org. 13. GSK, Wavre, Belgium. Electronic address: magali.x.traskine@gsk.com. 14. GSK, Wavre, Belgium. Electronic address: kristien.m.swinnen@gsk.com. 15. GSK, Wavre, Belgium. Electronic address: vincent.verlant@gsk.com. 16. GSK, Wavre, Belgium. Electronic address: dobbelaerekurt@gmail.com. 17. GSK, Wavre, Belgium. Electronic address: dorota.d.borys@gsk.com.
Abstract
BACKGROUND: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. METHODS: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. RESULTS:1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 μg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. CONCLUSION: Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872.
RCT Entities:
BACKGROUND: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. METHODS: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. RESULTS: 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 μg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. CONCLUSION: Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872.
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