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Constructing Mutants in Serotype 1 Streptococcus pneumoniae strain 519/43
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Human Infection Challenge with Serotype 3 Pneumococcus.

Ryan E Robinson1,2, Elena Mitsi1, Elissavet Nikolaou1

  • 1Clinical Sciences Department, Liverpool School of Tropical Medicine, Liverpool, UK.

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|July 8, 2022
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Summary
This summary is machine-generated.

A new human challenge model safely establishes Streptococcus pneumoniae serotype 3 (SPN3) nasopharyngeal colonization. This model, crucial for vaccine development, shows SPN3 carriage can cause mild upper respiratory symptoms.

Keywords:
SPN3challenge modelpneumococcusserotype 3

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Area of Science:

  • Infectious Diseases
  • Vaccinology
  • Microbiology

Background:

  • Streptococcus pneumoniae serotype 3 (SPN3) causes invasive disease and is less affected by PCV13 vaccination.
  • SPN3 incidence is rising in some populations, with a shift in circulating clades.
  • Human challenge models are vital for evaluating vaccine impact on upper airway colonization.

Purpose of the Study:

  • To establish a safe and feasible human challenge model for SPN3.
  • To determine SPN3's nasopharyngeal colonization ability using different clades and doses.
  • To assess the safety profile of the SPN3 challenge model.

Main Methods:

  • A human challenge study inoculated 96 healthy participants with three characterized SPN3 isolates (clades Ia, II, and no clade).
  • Inoculum doses were escalated to determine maximal colonization rates and safety.
  • Nasopharyngeal colonization was assessed via culture and molecular methods on days 2, 7, and 14.

Main Results:

  • Colonization rates varied from 30.0% to 70.0% depending on inoculum dose and isolate.
  • Mild symptoms, including sore throat, were reported by 30.0% of participants.
  • One participant developed otitis media; no serious adverse events were observed.

Conclusions:

  • A human challenge model for SPN3 is feasible and safe.
  • The SPN3 model demonstrates comparable carriage rates to existing models (e.g., Serotype 6B).
  • SPN3 nasopharyngeal carriage can lead to mild upper respiratory symptoms.