title: A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia.
abstract: BACKGROUND
  The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed.
  
  
  METHODS
  In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA.
  
  
  RESULTS
  Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study.
  
  
  CONCLUSIONS
  PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinically acceptable-safety profile.This study has been registered at http://www.clinicaltrials.govNCT00808444 and NCT01119625.
authors.affiliation: National Healthcare Group Polyclinics, 3 Fusionopolis Link #03-08, Nexus@one-north, Singapore 138543, Singapore. fong_seng_lim@nhgp.com.sg.
authors.forename: Fong Seng
authors.initials: FS
authors.lastname: Lim
authors.forename: Mia Tuang
authors.initials: MT
authors.lastname: Koh
authors.forename: Kah Kee
authors.initials: KK
authors.lastname: Tan
authors.forename: Poh Chong
authors.initials: PC
authors.lastname: Chan
authors.forename: Chia Yin
authors.initials: CY
authors.lastname: Chong
authors.forename: Yeo Wee
authors.initials: YW
authors.lastname: Shung Yehudi
authors.forename: Yee Leong
authors.initials: YL
authors.lastname: Teoh
authors.forename: Fakrudeen
authors.initials: F
authors.lastname: Shafi
authors.forename: Marjan
authors.initials: M
authors.lastname: Hezareh
authors.forename: Kristien
authors.initials: K
authors.lastname: Swinnen
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage; D002352:Carrier Proteins / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007072:Immunoglobulin D / Q000008:administration & dosage / Q000097:blood; D007223:Infant; D008074:Lipoproteins / Q000008:administration & dosage; D008296:Malaysia; D008297:Male; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012846:Singapore; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination; D064166:Vaccine Potency; D018074:Vaccines, Conjugate / Q000008:administration & dosage*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007072:Immunoglobulin D; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; C067989:glpQ protein, Haemophilus influenzae