Human Infection Challenge with Serotype 3 Pneumococcus.


Robinson, Ryan E, Mitsi, Elena, Nikolaou, Elissavet, Pojar, Sherin, Chen, Tao, Reiné, Jesús, 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

<h4>Rationale</h4>Streptococcus pneumoniae 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) programmes, 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.<h4>Objectives</h4>To establish SPN3's ability to colonise the nasopharynx using different inoculum clades and doses and the safety of an SPN3 challenge model.<h4>Methods</h4>In a human challenge study involving three well characterised and antibiotic sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade] and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, 160,000 CFU/100μL) were escalated until maximal colonisation rates were achieved, with concurrent acceptable safety.<h4>Outcome measures</h4>Presence and density of experimental SPN3 nasopharyngeal colonisation in nasal wash samples, assessed using microbiological culture and molecular methods, on days 2, 7 and 14 post-inoculation.<h4>Results</h4>96 healthy participants (median age 21, interquartile range 19-25) were inoculated (n=6-10 per dose group, 10 groups). Colonisation rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% sore throat, [24/29]), one developed otitis media requiring antibiotics. No serious adverse events occurred.<h4>Conclusions</h4>An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established SPN6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms. Clinical trial registration available at www. https://www.isrctn.com/, ID: ISRCTN11306486.

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: 16 Aug 2024 13:36
DOI: 10.1164/rccm.202112-2700oc
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3159165
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