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.

Abstract

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).

• Authors: Laura L Hammitt, James C Campbell, Dorota Borys, Robert C Weatherholtz, Raymond Reid, Novalene Goklish, Lawrence H Moulton, Magali Traskine, Yue Song, Kristien Swinnen, Mathuram Santosham, Katherine L O'Brien
• Journal: Vaccine (Vaccine) Vol. 37 Issue 51 Pg. 7482-7492 (12 03 2019) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 31629570 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• 13-valent pneumococcal vaccine
• Antibodies, Bacterial
• Bacterial Proteins
• Pneumococcal Vaccines
• Streptolysins
• Vaccines, Conjugate
• Vaccines, Subunit
• histidine triad protein
• plY protein, Streptococcus pneumoniae
• Hydrolases

Topics

• Acute Disease
• Antibodies, Bacterial (blood)
• Bacterial Proteins (administration & dosage, chemistry, immunology)
• Female
• Humans
• Hydrolases (administration & dosage, chemistry, immunology)
• Immunization Schedule
• Immunization, Secondary (methods)
• Immunogenicity, Vaccine
• Infant
• Infant, Newborn
• Male
• Otitis Media (immunology, microbiology, pathology, prevention & control)
• Patient Safety
• Pneumococcal Vaccines (administration & dosage, chemistry, immunology)
• Pneumonia, Pneumococcal (immunology, microbiology, pathology, prevention & control)
• Respiratory Tract Infections (immunology, microbiology, pathology, prevention & control)
• Streptococcus pneumoniae (immunology, pathogenicity)
• Streptolysins (administration & dosage, chemistry, immunology)
• Vaccines, Conjugate
• Vaccines, Subunit