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
Clinical Sciences Department, Liverpool School of Tropical Medicine, Liverpool, UK.
Respiratory Research Group, Liverpool University Hospitals Foundation Trust, Liverpool, UK.
Am J Respir Crit Care Med. 2022 Dec 1;206(11):1379-1392. 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.
3型血清型肺炎链球菌（SPN3）是侵袭性肺炎球菌疾病的病因之一，且携带率较低。在实施儿童13价肺炎球菌结合疫苗（PCV13）计划后，SPN3的下降幅度小于其他疫苗血清型，并且在一些人群中发病率有所上升，同时主要流行的SPN3进化枝从I型转变为II型。人体激发模型为评估PCV13对上呼吸道中SPN3的影响提供了一种有效手段。目的是确定SPN3使用不同接种进化枝和剂量在鼻咽部定植的能力，以及SPN3激发模型的安全性。在一项人体激发研究中，涉及三种特征明确且对抗生素敏感的SPN3分离株（PFESP306 [Ia进化枝]、PFESP231 [无进化枝]和PFESP505 [II进化枝]），接种剂量（10,000、20,000、80,000和160,000 cfu/100 μl）逐步增加，直至达到最大定植率，同时确保安全性可接受。在接种后第2、7和14天，使用微生物培养和分子方法评估鼻腔冲洗样本中实验性SPN3鼻咽部定植的存在情况和密度。总共96名健康参与者（中位年龄21岁，四分位间距19 - 25岁）接种了疫苗（每个剂量组6 - 10人，共10个组）。定植率在30.0% - 70.0%之间，因剂量和分离株而异。30.0%（29/96）报告有轻微症状（82.8% [24/29]出现喉咙痛）；1人发生需要使用抗生素治疗的中耳炎。未发生严重不良事件。SPN3人体激发模型是可行且安全的，其携带率与已建立的6B血清型人体激发模型相当。SPN3携带可能导致轻微的上呼吸道症状。
