A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants

Hum Vaccin Immunother. 2019;15(3):549-559. doi: 10.1080/21645515.2019.1568159. Epub 2019 Feb 15.

Abstract

Background: Two new formulations of an investigational 15-valent pneumococcal conjugate vaccine (PCV15-A and PCV15-B) were developed using 2 different protein-polysaccharide conjugation processes and evaluated in separate phase I/II studies (NCT02037984 [V114-004] and NCT02531373 [V114-005]) to assess optimal concentrations of pneumococcal polysaccharide (PnPs) and Aluminum Phosphate Adjuvant.

Methods: Various lots of PCV15-A and PCV15-B containing different concentrations of PnPs and/or adjuvant were compared to PCV13 in young adults and infants. Adults received single dose and infants received 4 doses at 2, 4, 6, and 12-15 months of age. Adverse events (AEs) were collected after each dose. Serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) were measured prior and 30 days postvaccination in adults, at 1 month postdose 3 (PD3), pre-dose4, and postdose 4 (PD4) in infants.

Results: Safety profiles were comparable across vaccination groups. At PD3, serotype-specific IgG GMCs were generally lower for either PCV15 formulation than PCV13 for most shared serotypes. PCV15 consistently elicited higher antibody responses to the 2 serotypes unique to the vaccine (22F and 33F) and serotype 3 for which PCV13 was shown to be ineffective. Except for serotypes 6A and 6B, no dose-response effect was observed with increasing concentrations of PnPs and/or adjuvant.

Conclusion: PCV15 is safe and induces IgG and OPA responses to all 15 serotypes in the vaccine. No significant differences in antibody responses were observed with increases in PnPs and/or Aluminum Phosphate Adjuvant.

Keywords: Pneumococcal conjugate vaccine; immunogenicity; safety.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood*
  • Dose-Response Relationship, Immunologic
  • Healthy Volunteers
  • Humans
  • Immunogenicity, Vaccine*
  • Immunoglobulin G / blood
  • Infant
  • Middle Aged
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / chemistry
  • Pneumococcal Vaccines / immunology*
  • Streptococcus pneumoniae / immunology*
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / chemistry
  • Vaccines, Conjugate / immunology
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • Vaccines, Conjugate

Grants and funding

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ (sponsor). Although the sponsor formally reviewed a penultimate draft, the opinions expressed are those of the authors and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript. The authors would like to acknowledge the assistance of Jon E. Stek and Daniel E. McCallus (both of Merck & Co., Inc., Kenilworth, NJ USA) for their editorial assistance.