Human Infection Challenge with Serotype 3 Pneumococcus

• Published in: American journal of respiratory and critical care medicine 2022-12, Vol.206 (11), p.1379-1392
• Main Authors: Robinson, Ryan E, Mitsi, Elena, Nikolaou, Elissavet, Pojar, Sherin, Chen, Tao, Reiné, Jesús, Nyazika, Tinashe K, Court, James, Davies, Kelly, Farrar, Madlen, Gonzalez-Dias, Patricia, Hamilton, Josh, Hill, Helen, Hitchins, Lisa, Howard, Ashleigh, Hyder-Wright, Angela, Lesosky, Maia, Liatsikos, Konstantinos, Matope, Agnes, McLenaghan, Daniella, Myerscough, Christopher, Murphy, Annabel, Solórzano, Carla, Wang, Duolao, Burhan, Hassan, Gautam, Manish, Begier, Elizabeth, Theilacker, Christian, Beavon, Rohini, Anderson, Annaliesa S, Gessner, Bradford D, Gordon, Stephen B, Collins, Andrea M, Ferreira, Daniela M
• Format: Article
• Language: English
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Carrier State; Child; Humans; Infant; Lung diseases; Nasopharynx - microbiology; Nose; Pathogenesis; Pediatrics; Pneumococcal Infections - prevention & control; Pneumococcal Vaccines - therapeutic use; Pneumonia; Serogroup; Streptococcus infections; Streptococcus pneumoniae; Throat; Vaccines; Young Adult
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.202112-2700OC

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. To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. 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. 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 (  = 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. 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.