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

BMC Infectious Diseases

Dorota Borys³  Kristien Swinnen³  Marjan Hezareh³  Fakrudeen Shafi⁸  Yee Leong Teoh⁵  Yeo Wee Shung Yehudi⁶  Chia Yin Chong¹  Poh Chong Chan⁷  Kah Kee Tan²  Mia Tuang Koh⁴  Fong Seng Lim⁶ 

[1] KK Women and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore;Departement of Pediatrics, Tuanku Ja’afar Hospital, Jalan Rasah, 70300 Seremban, Negeri Sembilan, Malaysia;Vaccine Discovery and Development, GlaxoSmithKline Vaccines, 20 Avenue Fleming, 1300 Wavre, Belgium;Departement of Pediatrics, University Malaya Medical Centre, Jalan University, 59100 Kuala Lumpur, Malaysia;Current affiliation: Goal Consultancy Asia Pacific, Singapore, Singapore;National Healthcare Group Polyclinics, 3 Fusionopolis Link #03-08, Nexus@one-north, Singapore 138543, Singapore;University Children's Medical Institute, National University Hospital, Singapore 119260, Singapore;GlaxoSmithKline Pharmaceuticals, 5 Embassy Links, SRT Road, Bangalore 560 052, India

关键词: Malaysia;    Singapore;    Toddler;    Infant;    Non-typeable Haemophilus influenzae;    Safety;    Immunogenicity;    Pneumococcal conjugate vaccine;   

Others  :  1125460
DOI  :  10.1186/1471-2334-14-530

 received in 2014-05-26, accepted in 2014-09-18,  发布年份 2014

【 摘 要 】

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.gov webciteNCT00808444 and NCT01119625.

【 授权许可】

   
2014 Lim et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 1.

Figure 3.

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