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.

BMJ Open
|November 25, 2025
PubMed

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.
Abstract

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