Elsevier

Vaccine

Volume 35, Issue 40, 25 September 2017, Pages 5331-5338
Vaccine

Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2–17-year-old children with asplenia or splenic dysfunction: A phase 3 study

https://doi.org/10.1016/j.vaccine.2017.08.039Get rights and content
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Highlights

  • Immunogenicity and safety of PHiD-CV was studied in 2–17-year-old at-risk children.

  • 46 children with asplenia or splenic dysfunction received 1 or 2 doses of PHiD-CV.

  • PHiD-CV was immunogenic in at-risk children and no safety concerns were identified.

Abstract

Background

Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population.

Methods

This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2–4, 5–10 and 11–17 years), was conducted in Poland and the Russian Federation. For the 2–4 years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2 months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31 days post-vaccination, respectively, and serious AEs (SAEs) throughout the study.

Results

Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2 µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child.

Conclusion

PHiD-CV was immunogenic and well tolerated in 2–17-year-old children with asplenia or splenic dysfunction.

Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.

Keywords

Pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV)
Immunogenicity
Safety
Asplenia
Splenic dysfunction

Abbreviations

AE
adverse event
ATP
according-to-protocol
CI
confidence interval
ELISA
enzyme-linked immunosorbent assay
22F-ELISA
enzyme-linked immunosorbent assay with serotype 22F polysaccharide adsorption
GMC
geometric mean concentration
GMT
geometric mean titer
IgG
immunoglobulin G
EL.U
ELISA units
LARs
legally acceptable representatives
NIP
national immunization program
OPA
opsonophagocytic activity
PCV
pneumococcal conjugate vaccine
PHiD-CV
pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine
PPSV23
23-valent pneumococcal plain polysaccharide vaccine
SCD
sickle cell disease
SAE
serious adverse event
TVC
total vaccinated cohort
ST
serotype
SD
standard deviation

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