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

Fong Seng Lim, Mia Tuang Koh, Kah Kee Tan, Poh Chong Chan, Chia Yin Chong, Yeo Wee Shung Yehudi, Yee Leong Teoh, Fakrudeen Shafi, Marjan Hezareh, Kristien Swinnen, Dorota Borys, Fong Seng Lim, Mia Tuang Koh, Kah Kee Tan, Poh Chong Chan, Chia Yin Chong, Yeo Wee Shung Yehudi, Yee Leong Teoh, Fakrudeen Shafi, Marjan Hezareh, Kristien Swinnen, Dorota Borys

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.

Figures

Figure 1
Figure 1
Trial profile. Clin = group of infants from Malaysia and Singapore who received the Phase III Clinical lot of PHiD-CV in the primary vaccination phase. Com = group of infants from Malaysia and Singapore who received the Commercial lot of PHiD-CV in the primary vaccination phase. ClinCom = group of toddlers from Singapore primed with the Phase III Clinical lot of PHiD-CV who received the Commercial lot of PHiD-CV in the booster vaccination phase. ComCom = group of toddlers from Singapore primed with the Commercial lot of PHiD-CV who received the Commercial lot of PHiD-CV in the booster vaccination phase.
Figure 2
Figure 2
Adjusted antibody GMC ratios between the Clin and the Com groups for the 10 vaccine pneumococcal serotypes and protein D at one month post-primary vaccination (primary ATP immunogenicity cohort). Clin = group of infants from Malaysia and Singapore who received the Phase III Clinical lot of PHiD-CV in the primary vaccination phase. Com = group of infants from Malaysia and Singapore who received the Commercial lot of PHiD-CV in the primary vaccination phase. Adjusted antibody GMC ratio = ratio of the geometric mean concentration at one month post-primary vaccination adjusted for country (pooled variance; Clin over Com group). PD = protein D. 95% CI = 95% confidence intervals (represented by the error bars). *Immunological non-inferiority was demonstrated if the upper limit of the 95% confidence interval of the adjusted antibody GMC ratio (Clin over Com) was below 2.0.
Figure 3
Figure 3
Solicited symptoms following (a) primary vaccination (overall/dose; primary TVC) and (b) booster dose (booster TVC). TVC = total vaccinated cohort. Clin = group of infants from Malaysia and Singapore who received the Phase III Clinical lot of PHiD-CV in the primary vaccination phase. Com = group of infants from Malaysia and Singapore who received the Commercial lot of PHiD-CV in the primary vaccination phase. ClinCom = group of toddlers from Singapore primed with the Phase III Clinical lot of PHiD-CV who received the Commercial lot of PHiD-CV in the booster vaccination phase. ComCom = group of toddlers from Singapore primed with the Commercial lot of PHiD-CV who received the Commercial lot of PHiD-CV in the booster vaccination phase. Error bars represent 95% confidence intervals. Solicited symptoms are recorded during 4-days post-vaccination.

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Pre-publication history
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