Human Infection Challenge with Serotype 3 Pneumococcus
Rationale: 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) 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. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: 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. Measurement and Main Results: 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 (n = 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. Conclusions: 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.
Errataetall: |
CommentIn: Am J Respir Crit Care Med. 2022 Dec 1;206(11):1312-1314. - PMID 35856830 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:206 |
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Enthalten in: |
American journal of respiratory and critical care medicine - 206(2022), 11 vom: 01. Dez., Seite 1379-1392 |
Sprache: |
Englisch |
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Links: |
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Themen: |
Anti-Bacterial Agents |
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Anmerkungen: |
Date Completed 02.12.2022 Date Revised 22.12.2022 published: Print CommentIn: Am J Respir Crit Care Med. 2022 Dec 1;206(11):1312-1314. - PMID 35856830 Citation Status MEDLINE |
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doi: |
10.1164/rccm.202112-2700OC |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM343233703 |
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245 | 1 | 0 | |a Human Infection Challenge with Serotype 3 Pneumococcus |
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500 | |a CommentIn: Am J Respir Crit Care Med. 2022 Dec 1;206(11):1312-1314. - PMID 35856830 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Rationale: 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) 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. Objectives: To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. Methods: 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. Measurement and Main Results: 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 (n = 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. Conclusions: 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a SPN3 | |
650 | 4 | |a challenge model | |
650 | 4 | |a pneumococcus | |
650 | 4 | |a serotype 3 | |
650 | 7 | |a Pneumococcal Vaccines |2 NLM | |
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700 | 1 | |a Nikolaou, Elissavet |e verfasserin |4 aut | |
700 | 1 | |a Pojar, Sherin |e verfasserin |4 aut | |
700 | 1 | |a Chen, Tao |e verfasserin |4 aut | |
700 | 1 | |a Reiné, Jesús |e verfasserin |4 aut | |
700 | 1 | |a Nyazika, Tinashe K |e verfasserin |4 aut | |
700 | 1 | |a Court, James |e verfasserin |4 aut | |
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700 | 1 | |a Hitchins, Lisa |e verfasserin |4 aut | |
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700 | 1 | |a Matope, Agnes |e verfasserin |4 aut | |
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700 | 1 | |a Solórzano, Carla |e verfasserin |4 aut | |
700 | 1 | |a Wang, Duolao |e verfasserin |4 aut | |
700 | 1 | |a Burhan, Hassan |e verfasserin |4 aut | |
700 | 1 | |a Gautam, Manish |e verfasserin |4 aut | |
700 | 1 | |a Begier, Elizabeth |e verfasserin |4 aut | |
700 | 1 | |a Theilacker, Christian |e verfasserin |4 aut | |
700 | 1 | |a Beavon, Rohini |e verfasserin |4 aut | |
700 | 1 | |a Anderson, Annaliesa S |e verfasserin |4 aut | |
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