Efficacy, safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: A phase IIb randomized study.
Acute Disease
Antibodies, Bacterial
/ blood
Bacterial Proteins
/ administration & dosage
Female
Humans
Hydrolases
/ administration & dosage
Immunization Schedule
Immunization, Secondary
/ methods
Immunogenicity, Vaccine
Infant
Infant, Newborn
Male
Otitis Media
/ immunology
Patient Safety
Pneumococcal Vaccines
/ administration & dosage
Pneumonia, Pneumococcal
/ immunology
Respiratory Tract Infections
/ immunology
Streptococcus pneumoniae
/ immunology
Streptolysins
/ administration & dosage
Vaccines, Conjugate
Vaccines, Subunit
Acute otitis media
Immunogenicity
Native American
Reactogenicity
Streptococcus pneumoniae
Vaccines
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
03 12 2019
03 12 2019
Historique:
received:
11
06
2019
revised:
18
09
2019
accepted:
20
09
2019
pubmed:
21
10
2019
medline:
30
9
2020
entrez:
21
10
2019
Statut:
ppublish
Résumé
Native American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs. In this phase IIb, double-blind, controlled trial, 6-12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12-15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children. 1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: -11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (-9.5, 14.0) and 5.2% (-8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between -4.4% (-39.2, 21.8) and 2.0% (-18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants. The dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated. NCT01545375 (www.clinicaltrials.gov).
Sections du résumé
BACKGROUND
Native American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs.
METHODS
In this phase IIb, double-blind, controlled trial, 6-12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12-15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children.
RESULTS
1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: -11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (-9.5, 14.0) and 5.2% (-8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between -4.4% (-39.2, 21.8) and 2.0% (-18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants.
CONCLUSIONS
The dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated.
CLINICAL TRIALS REGISTRATION
NCT01545375 (www.clinicaltrials.gov).
Identifiants
pubmed: 31629570
pii: S0264-410X(19)31304-0
doi: 10.1016/j.vaccine.2019.09.076
pii:
doi:
Substances chimiques
13-valent pneumococcal vaccine
0
Antibodies, Bacterial
0
Bacterial Proteins
0
Pneumococcal Vaccines
0
Streptolysins
0
Vaccines, Conjugate
0
Vaccines, Subunit
0
histidine triad protein
0
plY protein, Streptococcus pneumoniae
0
Hydrolases
EC 3.-
Banques de données
ClinicalTrials.gov
['NCT01545375']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7482-7492Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.