Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3)

作者：Phoebe Hazenberg, Ryan Robinson, Madlen Farrar, Carla Solórzano, Angela Hyder-Wright, Konstantinos Liatsikos, J Brunning, Hannah Fleet, Amy Bettam, Ashleigh Howard, Tinashe Kenny-Nyazika, Britta C. Urban, Elena Mitsi, Dima El Safadi, Kelly Davies, Maia Lesosky, Stephen B. Gordon, Daniela M. Ferreira, Andrea M. Collins · 发表于：BMJ Open · 年份：2024 · DOI：10.1136/bmjopen-2023-075948 · 被引用次数：7 · 研究领域：Pneumonia and Respiratory Infections、Respiratory viral infections research、vaccines and immunoinformatics approaches

INTRODUCTION: Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size. METHODS AND ANALYSIS: This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of th...