Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study
| Autor: | Mark R. Alderson, Kurt Dobbelaere, Magali Traskine, Ezra O. Ogundare, Yauba Saidu, Brian Greenwood, Isatou Drammeh, Abdoulie Bojang, Sonia Schoonbroodt, Kristien Swinnen, Archibald Worwui, Beate Kampmann, Olumuyiwa Owolabi, Vincent Verlant, Martin Antonio, Nathalie Devos, Fatima Ceesay, Sheikh Jarju, Martin O. C. Ota, Ebenezer Foster-Nyarko, Dorota Borys, Aderonke Odutola, Olubukola T. Idoko, Patrick K. Owiafe |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Dose-Response Relationship Immunologic medicine.disease_cause Pneumococcal conjugate vaccine Pneumococcal Infections Pneumococcal Vaccines 03 medical and health sciences 0302 clinical medicine Bacterial Proteins Nasopharynx Streptococcus pneumoniae medicine Humans Single-Blind Method 030212 general & internal medicine Reactogenicity Pneumolysin General Veterinary General Immunology and Microbiology business.industry Public Health Environmental and Occupational Health Toxoid Infant Vaccine efficacy Bacterial Load 030104 developmental biology Infectious Diseases Carriage Treatment Outcome Pneumococcal vaccine Immunology Carrier State Molecular Medicine Female Gambia business medicine.drug |
| ISSN: | 0264-410X |
| Popis: | Background Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30 μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. Methods In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8–10 weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30 μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2–3–4 months (3 + 0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2–4–9 months (2 + 1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5–9–12 months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. Results 1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60–67%) and non-10VT (55–61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3 + 0 schedule) was 1.1% (95% CI −21.5, 19.5) and 2.1% (−20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2 + 1 schedule) was 0.5% (−22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. Conclusions In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints. Funding: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872 . |
| Databáze: | OpenAIRE |
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