Human Infection Challenge with Serotype 3 Pneumococcus



Robinson, Ryan E, Mitsi, Elena, Nikolaou, Elissavet, Pojar, Sherin, Chen, Tao ORCID: 0000-0002-5489-6450, Reine, Jesus, Nyazika, Tinashe K, Court, James, Davies, Kelly, Farrar, Madlen
et al (show 24 more authors) (2022) Human Infection Challenge with Serotype 3 Pneumococcus. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 206 (11). pp. 1379-1392.

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Abstract

<b>Rationale:</b> <i>Streptococcus pneumoniae</i> serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. <b>Objectives:</b> To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. <b>Methods:</b> In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 μl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. <b>Measurement and Main Results:</b> Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated (<i>n</i> = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. <b>Conclusions:</b> An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.

Item Type: Article
Uncontrolled Keywords: pneumococcus, serotype 3, challenge model, SPN3
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 22 Jul 2022 13:58
Last Modified: 08 Jul 2023 01:30
DOI: 10.1164/rccm.202112-2700OC
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3159165