Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial

Abstract

Background: Pneumonia is still the leading cause of death among children in Africa, and pneumococcal serotypes 1 and 5 are frequently isolated from African children with invasive pneumococcal disease below the age of 5 years. The immunogenicity, safety and reactogenicity of 3-dose primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in infants in Mali and Nigeria.

Methods: In an open, randomized, controlled study, 357 infants received DTPw-HBV/Hib and OPV primary vaccination with (PHiD-CV group) or without (control group) PHiD-CV co-administration at 6, 10 and 14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured and adverse events (AEs) recorded.

Results: One month post-dose 3, ≥ 97.2% of PHiD-CV-vaccinated infants had an antibody concentration ≥ 0.2 μg/mL for each vaccine pneumococcal serotype except for 6B (82.0%) and 23F (87.6%) versus < 10% in the control group except for serotypes 14 (35.7%) and 19F (22.5%). For each vaccine serotype, ≥ 93.3% of PHiD-CV recipients had an OPA titre ≥ 8, except for serotypes 1 (87.6%) and 6B (85.4%), compared to < 10% in the control group, except for serotypes 7F (42.9%), 9V (24.1%) and 14 (24.5%). Anti-protein D geometric mean antibody concentrations were 3791.8 and 85.4 EL.U/mL in the PHiD-CV and control groups, respectively. Overall incidences of solicited and unsolicited AEs were similar between groups.

Conclusions: In sub-Saharan African infants, PHiD-CV was immunogenic for all vaccine pneumococcal serotypes and protein D. Vaccine tolerability was generally comparable between the PHiD-CV and control groups.

Trial registration: ClinicalTrials.gov identifier: NCT00678301.

Figure 1

Trial profile.

Figure 2

Local symptoms. Percentage of doses followed by pain (A), redness (B) and swelling (C) at the specified injection site of any intensity and grade 3 intensity (hatched areas) (ATP immunogenicity cohort). Error bars indicate 95% CIs. Grade 3 pain: crying when limb was moved/spontaneously painful; grade 3 redness/swelling: diameter > 30 mm.

Figure 3

General symptoms. Percentage of doses followed by drowsiness (A), fever (B), irritability (C) and loss of appetite (D) of any intensity and grade 3 intensity (hatched areas) (ATP immunogenicity cohort). Error bars indicate 95% CIs. Grade 3 drowsiness: prevented normal activity; grade 3 fever: axillary temperature > 39.5°C; grade 3 irritability: crying that could not be comforted/prevented normal activity; grade 3 loss of appetite: child did not eat at all.