Safety and immunogenicity of a novel 10-valent pneumococcal conjugate vaccine candidate in adults, toddlers, and infants in The Gambia—Results of a phase 1/2 randomized, double-blinded, controlled trial

• Published in: Vaccine 2020-01, Vol.38 (2), p.399-410
• Main Authors: Clarke, Ed, Bashorun, Adedapo O., Okoye, Michael, Umesi, Ama, Badjie Hydara, Mariama, Adigweme, Ikechukwu, Dhere, Rajeev, Sethna, Vistasp, Kampmann, Beate, Goldblatt, David, Tate, Andi, Weiner, Debra H, Flores, Jorge, Alderson, Mark R., Lamola, Steve
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adults; Age; Aluminum; Babies; Conjugates; Consent; Double-Blind Method; Evaluation; Female; Fever; Gambia; Humans; Hypothesis testing; Immune response; Immunization; Immunization Programs; Immunization Schedule; Immunization, Secondary - methods; Immunogenicity; Immunoglobulin G; Infant; Infants; Laboratories; Licenses; Male; Morbidity; Mortality; Nurses; Phase 1/2; Pneumococcal conjugate vaccine; Pneumococcal Infections - immunology; Pneumococcal Infections - prevention & control; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - adverse effects; Pneumococcal Vaccines - immunology; Pneumonia; Preschool children; Randomization; Reactogenicity; Safety; Serotypes; Streptococcus infections; Toddler; Toddlers; Tolerability; Vaccination; Vaccines; Whooping cough; Young Adult
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.08.072

•Safe, effective and more affordable pneumococcal conjugate vaccines (PCV) are needed.•This new PCV targets serotypes most likely to cause disease in low- and middle-income countries.•The vaccine was safe and immunogenic in adults, toddlers and infants in this phase 1/2 trial.•The data support progression to a phase 3 licensure trial of the new PCV. A more affordable pneumococcal conjugate vaccine (PCV) that provides comparable protection to current PCVs is needed to ensure sustainable access in resource-limited settings. Serum Institute of India Pvt. Ltd.’s PCV candidate (SIIPL-PCV) has the potential to meet this need as manufacturing efficiency has been optimized and the vaccine targets the most prevalent disease-causing serotypes in Africa and Asia. We report SIIPL-PCV’s safety, tolerability, and immunogenicity in adults, toddlers, and infants in The Gambia. This phase 1/2, randomized, double-blind trial sequentially enrolled 34 PCV-naive adults (18–40 years old), 112 PCV (Prevenar 13® [PCV13])-primed toddlers (12–15 months old), and 200 PCV-naive infants (6–8 weeks old), who were randomized (1:1) to receive SIIPL-PCV or a licensed comparator vaccine. Infants received three-doses of SIIPL-PCV or PCV13 at 6, 10, and 14 weeks of age co-administered with routine Expanded Program on Immunization (EPI) vaccines. Reactogenicity was solicited through seven-days post-vaccination; unsolicited adverse events (AEs) were assessed throughout the study. The safety and immunogenicity of a matching booster at 10–14 months of age were evaluated in a subset of 96 infants. Immune responses were evaluated post-primary and pre- and post-booster vaccinations. Reactogenicity was primarily mild-to-moderate in severity. In infants, the most common solicited reactions were injection-site tenderness and fever, with no meaningful treatment-group differences. There were no serious or severe vaccine-related AEs and no meaningful trends in SAEs, vaccine-related AEs, or overall AEs. Infant post-primary seroresponse rates (IgG level ≥ 0.35 µg/mL) were ≥89% for all serotypes except 6A (79%) in the SIIPL-PCV group. IgG GMCs were >1 µg/mL for all serotypes in both SIIPL-PCV and PCV13 groups. Post-booster GMCs were comparable between groups. SIIPL-PCV was well-tolerated, had an acceptable safety profile, and was immunogenic for all vaccine serotypes. Results support the evaluation of SIIPL-PCV in a phase 3 non-inferiority trial. Clinicaltrials.gov: NCT02308540.