Journal Article

Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study

Kampmann, Beate, Ota, Martin O.C., Worwui, Archibald, Drammeh, Isatou, Swinnen, Kristien, Dobbelaere, Kurt, Saidu, Yauba, Jarju, Sheikh, Verlant, Vincent, Greenwood, Brian M., Idoko, Olubukola T., Devos, Nathalie, Owolabi, Olumuyiwa, Schoonbroodt, Sonia, Owiafe, Patrick K., Bojang, Abdoulie, Ceesay, Fatima, Borys, Dorota, Alderson, Mark, Odutola, Aderonke, Antonio, Martin, Ogundare, Ezra O., Traskine, Magali, Foster-Nyarko, Ebenezer

2017

Overview

•Pneumococcal protein antigens could provide serotype-independent protection.•Two PHiD-CV/dPly/PhtD vaccine formulations were assessed in healthy infants.•Both protein-based vaccines elicited immune responses to pneumococcal proteins.•The vaccines had no impact on pneumococcal nasopharyngeal carriage prevalence.•Future evaluations will assess their impact against pneumococcal disease endpoints. 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 (30μg 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. In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8–10weeks, 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 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2–3–4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2–4–9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5–9–12months. 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. 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. 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Age / Allergy and Immunology / Aluminum / Antigens / Babies / Bacterial Load / Bacterial Proteins - administration & dosage / Bacterial Proteins - immunology / Bacterial Proteins - toxicity / Carrier State - prevention & control / Children / Combined vaccines / Conjugates / Disease / Dose-Response Relationship, Immunologic / Double-blind studies / Effectiveness / Female / Gambia / Histidine / Humans / Immune clearance / Immune response / Immunoglobulins / Infant / Infants / Laboratories / Male / microbial load / Nasopharyngeal carriage / Nasopharynx - microbiology / Pneumococcal histidine triad protein D / Pneumococcal Infections - prevention & control / Pneumococcal Vaccines - administration & dosage / Pneumococcal Vaccines - adverse effects / Pneumococcal Vaccines - genetics / Pneumococcal Vaccines - immunology / Pneumolysin / Pneumonia / Polysaccharides / Protein D / Proteins / Schedules / sequence analysis / Single-Blind Method / Streptococcus infections / Streptococcus pneumoniae / Streptococcus pneumoniae - immunology / Streptococcus pneumoniae - isolation & purification / Treatment Outcome / Vaccine efficacy / Vaccines / Womens health