A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzaeprotein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia

Abstract

BackgroundThe 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.MethodsIn 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.ResultsImmune 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.ConclusionsPHiD-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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-530) contains supplementary material, which is available to authorized users.

Safety of routine childhood vaccine coadministration versus separate vaccination

“…Fever, local and general symptoms, and gastrointestinal events were often reported in another study on DTaP/IPV/Hib+PCV+RV coadministration 37. Also studies on DTaP/IPV/Hib/HepB+PCV+RV reported mostly fever, local reactions, respiratory and gastrointestinal events 38 39. MMR+Hib/MenC+PCV led to more gastrointestinal, and respiratory events and less fever and musculoskeletal events than would have been expected based on separate vaccinations.…”

Brief communication: immunogenicity of measles vaccine when co-administered with 10-valent pneumococcal conjugate vaccine

“…PCV10 co-administration has previously been reported not to impact on the immunogenicity or reactogenicity of other childhood vaccines such as Infanrix™-IPV/Hib (diphtheria-tetanus-acellular pertussis-inactivated poliovirus-H. influenzae type b) or Infanrix™ hexa (Infanrix™-IPV/Hib with hepatitis B antigens), and Rotarix™ (live attenuated human rotavirus vaccine) [7][8][9] . Data on the coadministration of PCV and MV are limited, particularly for Asian countries.…”