Human Infection Challenge with Serotype 3 Pneumococcus
Ryan Robinson, Elena Mitsi, Elissavet Nikolaou, Sherin Pojar, Tao Chen, Jesús Reiné, Tinashe K. Nyazika, James Court, Kelly Davies, Madlen Farrar, Patrícia Gonzalez‐Dias, Josh Hamilton, Helen Hill, Lisa Hitchins, Ashleigh Howard, Angela Hyder-Wright, Maia Lesosky, Konstantinos Liatsikos, Agnes Matope, Daniella McLenaghan, Christopher Myerscough, Annabel Murphy, Carla Solórzano, Duolao Wang, Hassan Burhan, Manish Gautam, Elizabeth Begier, Christian Theilacker, Rohini Beavon, Annaliesa S. Anderson, Bradford D. Gessner, Stephen B. Gordon, Andrea M. Collins, Daniela M. Ferreira
Abstract
Abstract 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.