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

•Protein antigens could offer serotype-independent protection against pneumococcal infection.•dPly/PhtD was assessed in healthy Native American infants when co-administered with PCV13.•Vaccine efficacy against AOM and ALRI was evaluated.•dPly/PhtD was immunogenic but incremental efficacy against AOM...

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Published in:Vaccine 2019-12, Vol.37 (51), p.7482-7492
Main Authors: Hammitt, Laura L., Campbell, James C., Borys, Dorota, Weatherholtz, Robert C., Reid, Raymond, Goklish, Novalene, Moulton, Lawrence H., Traskine, Magali, Song, Yue, Swinnen, Kristien, Santosham, Mathuram, O'Brien, Katherine L.
Format: Article
Language:English
Subjects:
Acute otitis media
Aluminum
Antigens
Children
Clinical trials
Confidence intervals
Conjugates
Ear diseases
Estimates
Fever
Health services
Histidine
Immunization
Immunogenicity
Infants
Influenza
Minority & ethnic groups
Native American
Native North Americans
Otitis media
Pediatrics
Pneumolysin
Population studies
Protein D
Proteins
Randomization
Reactogenicity
Respiratory tract
Respiratory tract diseases
Safety
Schedules
Streptococcus infections
Streptococcus pneumoniae
Vaccine efficacy
Vaccines
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Summary:•Protein antigens could offer serotype-independent protection against pneumococcal infection.•dPly/PhtD was assessed in healthy Native American infants when co-administered with PCV13.•Vaccine efficacy against AOM and ALRI was evaluated.•dPly/PhtD was immunogenic but incremental efficacy against AOM over PCV13 was not demonstrated. 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)
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2019.09.076