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

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

Research output: Contribution to journalArticle

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)

Original languageEnglish (US)
JournalVaccine
DOIs
StateAccepted/In press - Jan 1 2019

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otitis media
Conjugate Vaccines
Otitis Media
Vaccines
immune response
vaccines
Safety
Pneumococcal Vaccines
North American Indians
Proteins
proteins
American Indians
Pediatrics
Respiratory Tract Infections
Confidence Intervals
Immunization Schedule
Toxoids
13-valent pneumococcal vaccine
respiratory tract diseases
confidence interval

Keywords

  • Acute otitis media
  • Immunogenicity
  • Native American
  • Reactogenicity
  • Streptococcus pneumoniae
  • Vaccines

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

@article{3513f2813b834c27a632fe4ea42b5f99,
title = "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)",
keywords = "Acute otitis media, Immunogenicity, Native American, Reactogenicity, Streptococcus pneumoniae, Vaccines",
author = "Hammitt, {Laura L.} and Campbell, {James C.} and Dorota Borys and Weatherholtz, {Robert C.} and Raymond Reid and Novalene Goklish and Moulton, {Lawrence H.} and Magali Traskine and Yue Song and Kristien Swinnen and Mathuram Santosham and O'Brien, {Katherine L.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.vaccine.2019.09.076",
language = "English (US)",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - 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

T2 - A phase IIb randomized study

AU - Hammitt, Laura L.

AU - Campbell, James C.

AU - Borys, Dorota

AU - Weatherholtz, Robert C.

AU - Reid, Raymond

AU - Goklish, Novalene

AU - Moulton, Lawrence H.

AU - Traskine, Magali

AU - Song, Yue

AU - Swinnen, Kristien

AU - Santosham, Mathuram

AU - O'Brien, Katherine L.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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)

AB - 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)

KW - Acute otitis media

KW - Immunogenicity

KW - Native American

KW - Reactogenicity

KW - Streptococcus pneumoniae

KW - Vaccines

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U2 - 10.1016/j.vaccine.2019.09.076

DO - 10.1016/j.vaccine.2019.09.076

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JO - Vaccine

JF - Vaccine

SN - 0264-410X

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