Safety, tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

Vaccine. 2023 Apr 6;41(15):2456-2465. doi: 10.1016/j.vaccine.2023.02.041. Epub 2023 Feb 24.

Abstract

Background: This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F.

Methods: Healthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F.

Results: 1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 μg/mL (lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose. Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates.

Conclusion: A two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F.

Trial registration: ClinicalTrials.gov NCT04016714.

Keywords: Child; Clinical trial; Infant; Pneumococcal infections; Pneumococcal vaccines.

Publication types

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

MeSH terms

  • Antibodies, Bacterial
  • Haemophilus influenzae type b*
  • Hepatitis B Vaccines
  • Humans
  • Immunogenicity, Vaccine
  • Immunoglobulin G
  • Infant
  • Pneumococcal Infections* / prevention & control
  • Pneumococcal Vaccines
  • Streptococcus pneumoniae
  • Tetanus Toxoid
  • Tetanus*
  • Vaccines, Conjugate

Substances

  • Pneumococcal Vaccines
  • gamma-hydroxy-gamma-ethyl-gamma-phenylbutyramide
  • Antibodies, Bacterial
  • Tetanus Toxoid
  • Vaccines, Conjugate
  • Hepatitis B Vaccines
  • Immunoglobulin G

Associated data

  • ClinicalTrials.gov/NCT04016714
  • EudraCT/EudraCT 2018–003788-70