Immunogenicity and safety of 11- and 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccines (11vPHiD-CV, 12vPHiD-CV) in infants: Results from a phase II, randomised, multicentre study

Vaccine. 2019 Jan 3;37(1):176-186. doi: 10.1016/j.vaccine.2018.07.023. Epub 2018 Jul 24.


Background: We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent).

Methods: In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 μg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed.

Results: 951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded.

Conclusion: Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.

Keywords: Immunogenicity; Infants/children; Non-inferiority; PHiD-CV; Pneumococcal conjugate vaccine; Safety.

Publication types

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

MeSH terms

  • Antibodies, Bacterial / blood*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Female
  • Haemophilus influenzae
  • Hepatitis B Vaccines / administration & dosage
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine*
  • Immunoglobulin D / genetics
  • Immunoglobulin D / immunology*
  • Infant
  • Lipoproteins / genetics
  • Lipoproteins / immunology*
  • Male
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines / adverse effects
  • Pneumococcal Vaccines / immunology*
  • Poliovirus Vaccine, Inactivated / administration & dosage
  • Serogroup
  • Streptococcus pneumoniae
  • Vaccines, Combined / administration & dosage
  • Vaccines, Conjugate / adverse effects
  • Vaccines, Conjugate / immunology


  • Antibodies, Bacterial
  • Bacterial Proteins
  • Carrier Proteins
  • DTPa-HBV-IPV combined vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Hepatitis B Vaccines
  • Immunoglobulin D
  • Lipoproteins
  • Pneumococcal Vaccines
  • Poliovirus Vaccine, Inactivated
  • Vaccines, Combined
  • Vaccines, Conjugate
  • glpQ protein, Haemophilus influenzae