A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi - A feasibility study.
A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi - A feasibility study.
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马拉维的肺炎球菌控制人类感染模型：将已建立的肺炎球菌携带模型从英国利物浦转移到马拉维布兰太尔 - 可行性研究。
DOI：
10.12688/wellcomeopenres.15689.1
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发表时间：
2020
影响因子：
--
通讯作者：
S. Gordon
中科院分区：
文献类型：
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作者：
B. Morton;S. Burr;K. Jambo;J. Rylance;M. Henrion;N. Banda;E. Nsomba;Blessings M. Kapumba;L. Manda;C. Masesa;Daniela Ferrreira;S. Gordon
肺炎链球菌是世界范围内社区获得性肺炎、细菌性脑膜炎和菌血症的主要致病和死亡原因。肺炎球菌结合疫苗可预防侵袭性疾病，但制造成本高，血清型覆盖有限，与血清型替换有关，并显示出对抗粘膜定植的有效性降低。由于无症状的鼻咽定植是肺炎球菌疾病的先决条件，这被建议作为新疫苗疗效的标志。我们的团队在利物浦热带医学院(LSTM)建立了一个安全和可重复性的肺炎球菌控制的人类感染模型。十年来，它已经被用来在1000多名参与者中测试疫苗对鼻咽携带者的保护作用。我们将把已建立的标准化操作程序从LSTM转移到马拉维，并在多达36名健康参与者中进行测试。主要终点：肺炎球菌攻击后从受试者鼻腔冲洗中采集的经典培养物检测接种的肺炎球菌。次级终点：确认用于样本捕获和处理的可靠的临床和实验室方法。第三终点：研究和方法的受试者可接受性。我们将测试三种剂量的肺炎球菌疫苗(每个鼻孔20,000，80,000和160,000个集落形成单位[CFU])，采用简约的研究设计，旨在减少对参与者的不必要接触。我们假设，根据已建立的LSTM实践，80,000个CFU将在大约一半的参与者中诱导鼻腔定植。可行性研究的目的是：1)在马拉维建立肺炎链球菌试验性人类肺炎球菌携带者；2)确定最佳鼻咽肺炎球菌激发剂量；3)确认安全性并测量潜在症状；4)确认抽样方案和实验室化验；5)评估同意和研究程序的可行性和可接受性。在马拉维确认肺炎球菌控制的人类感染模式的可行性，将使我们能够针对高危人群的肺炎球菌疫苗候选者，他们将从新的和改进的疫苗战略中获益最多。
Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation. As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.