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Updated: Jul 14, 2026

Experimental Human Pneumococcal Carriage
Published on: February 15, 2013
Protocol for a phase IV, Experimental Human Pneumococcal Challenge (EHPC) model to investigate Streptococcus
Bruno Rocha de Macedo1, Carla Solórzano1, Angela Hyder-Wright2,3
1Department of Paediatrics, University of Oxford, Oxford, UK.
Insights
This study investigates if VAXNEUVANCE (PCV15) reduces Streptococcus pneumoniae serotype 3 (SPN3) carriage in adults. The controlled human infection model assesses SPN3 acquisition, density, and duration post-vaccination.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Streptococcus pneumoniae serotype 3 (SPN3) causes significant invasive pneumococcal disease globally.
- Current vaccines offer limited protection against SPN3, necessitating improved vaccine strategies.
- A controlled human infection model provides a robust platform to evaluate vaccine efficacy against specific pneumococcal serotypes.
Purpose of the Study:
- To assess the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine, PCV15) on SPN3 carriage acquisition, density, and duration.
- To compare immune responses elicited by PCV15 versus placebo in healthy adults.
- To explore gene expression changes in nasal tissue following PCV15 vaccination.
Main Methods:
- A double-blind, randomized controlled trial involving healthy adults aged 18-50 years.
- Participants receive either PCV15 or placebo, followed by intranasal inoculation with SPN3 one month later.
- Monitoring includes safety, SPN3 colonization status, density, duration, and immune responses over 28 days. Exploratory nasal biopsies will assess gene expression.
Main Results:
- Primary endpoint: Rate of SPN3 acquisition in PCV15 recipients versus placebo.
- Secondary endpoints: Density and duration of SPN3 colonization, comparative immune responses.
- Exploratory analysis: Gene expression changes in nasal tissue post-PCV15 vaccination.
Conclusions:
- The study will determine if PCV15 can effectively reduce SPN3 carriage.
- Findings will inform the development of next-generation pneumococcal vaccines.
- Understanding the impact on carriage may lead to reduced disease burden.
Introduction:
Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model.
Methods And Analysis:
Healthy adults aged 18-50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue.
Ethics And Dissemination:
This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).
Trial Registration Number:
NCT06731374 - ISRCTN91656864.
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