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O046 - FIRST HUMAN INFECTION CHALLENGE STUDY WITH SEROTYPE 3 PNEUMOCOCCUS: SELECTING AN OPTIMAL CHALLENGE ISOLATE, DOSE RANGING AND ESTABLISHING SAFETY (ID 196)
Abstract
Background
Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programmes, the decline in serotype 3 (SPN3) has been less than for other vaccine serotypes and in some settings incidence has increased, coincident with a shift in the main circulating SPN3 clade, from I to II. The development of a novel SPN3 human challenge model will allow the interaction between PCV13 and SPN3 in the upper airway to be investigated.
Methods
A human challenge study involving three well characterized and antibiotic sensitive isolates of SPN3 (PFESP306 [clade Ia], PFESP231 [no clade] and PFESP505 [clade II]). Isolates were selected based on antibiotic sensitivity, phylogenesis, clade affiliation, presence of virulence/colonization genes, and pneumococcal chain length in liquid culture, the latter positively correlating with achieved average human experimental pneumococcal colonization rates. Doses were escalated (10,000cfu- 160,000 cfu) until maximal colonization rates with concurrent acceptable safety were achieved. Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples were assessed using microbiological and molecular methods, on days 2, 7 and 14 post-inoculation.
Results
96 healthy participants (median age 21, interquartile range 19-25) were inoculated, with all isolates efficiently and safely colonising the nasopharynx. Colonisation rates were 30.0-70.0% based on dose/isolate. 30% (29/96) reported mild symptoms (82.8% sore throat, [24/29]) with the majority at higher doses. There were no serious adverse events.
Conclusions
An SPN3 human challenge model is feasible and safe with comparable carriage rates to a SPN6B model. SPN3 carriage may cause mild upper respiratory symptoms.