Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study

Alassane Dicko, Yahia Dicko, Amadou Barry, Youssoufa Sidibe, Almahamoudou Mahamar, Gaoussou Santara, Amagana Dolo, Aminata Diallo, Ogobara Doumbo, Fakrudeen Shafi, Nancy François, Juan Pablo Yarzabal, Ana Strezova, Dorota Borys, Lode Schuerman, Alassane Dicko, Yahia Dicko, Amadou Barry, Youssoufa Sidibe, Almahamoudou Mahamar, Gaoussou Santara, Amagana Dolo, Aminata Diallo, Ogobara Doumbo, Fakrudeen Shafi, Nancy François, Juan Pablo Yarzabal, Ana Strezova, Dorota Borys, Lode Schuerman

Abstract

Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children.

Keywords: 22F-ELISA, 22F-inhibition enzyme-linked immunosorbent assay; 7vCRM, 7-valent pneumococcal CRM197 conjugate vaccine; AE, adverse event; ATP, according-to-protocol; CI, confidence interval; DTPw-HBV/Hib, diphtheria-tetanus-whole-cell pertussis, hepatitis B virus/Haemophilus influenzae type b vaccine; EL.U, ELISA unit; GAVI, Global Alliance for Vaccines and Immunization; GMC, geometric mean concentration; GMT, geometric mean titer; IPD, invasive pneumococcal disease; IgG, immunoglobulin G; LAR, legally acceptable representative; Mali; NTHi, non-typeable Haemophilus influenzae; OPA, opsonophagocytic activity; OPV, oral live attenuated poliovirus vaccine; PCV, pneumococcal conjugate vaccine; PHiD-CV; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine; SAE, serious adverse event; SD, standard deviation; catch-up vaccination; immunogenicity; pneumococcal conjugate vaccine; reactogenicity; safety.

Figures

Figure 1.
Figure 1.
Trial profile. Footnote: N = number of subjects; ATP, according-to-protocol.

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