Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children: Booster dose and 2-dose catch-up regimens in the second year of life

Abstract

In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15-21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ≥ 0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ≥ 8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ≥ 0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ≥8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D.

Keywords: Nigeria; PHiD-CV; booster; catch-up; immunogenicity; pneumococcal conjugate vaccine; reactogenicity; safety.

Figures

Figure 1. Trial profile. Note: An issue was identified with the informed consent obtained for one child and the child’s parents didn’t permit GlaxoSmithKline Vaccines to use the child’s data. As a result, the data of the child, who had an SAE that was not considered to be related to the study medication by the investigator, are not detailed and were not used in the analysis.

Figure 2. (A) Geometric mean antibody concentrations (GlaxoSmithKline’s 22F-inhibition ELISA, binary logarithmic scale, ATP cohort for immunogenicity) and (B) opsonophagocytic geometric mean titers against individual pneumococcal serotypes (decimal logarithmic scale, ATP cohort for immunogenicity). Note: Post-pri, 1 mo after 3-dose priming (at approximately 5 mo of age) with PHiD-CV in PHiD-CV booster group and control vaccine in PHiD-CV catch-up group; Pre-bst/catch-up, before booster dose in PHiD-CV booster group or before first catch-up dose in PHiD-CV catch-up group (15 to 21 mo of age); Post-bst/catch-up, 1 mo after booster dose in PHiD-CV booster group (16 to 22 mo of age) or 1 mo after second catch-up dose in PHiD-CV catch-up group (18 to 24 mo of age). Error bars represent 95% confidence intervals.

Figure 3. ELISA antibody responses (with 95% confidence intervals) against protein D (logarithmic scale, ATP cohort for immunogenicity). Note: Post-priming, 1 mo after 3-dose priming (at approximately 5 mo of age) with PHiD-CV in PHiD-CV booster group and control vaccine in PHiD-CV catch-up group; Pre-booster/catch-up, before booster dose in PHiD-CV booster group or before first catch-up dose in PHiD-CV catch-up group (15 to 21 mo of age); Post-booster/catch-up, 1 mo after booster dose in PHiD-CV booster group (16 to 22 mo of age) or 1 mo after second catch-up dose in PHiD-CV catch-up group (18 to 24 mo of age).