Integrating genomic surveillance and ecological modelling to maximise pneumococcal vaccine efficacy

整合基因组监测和生态模型以最大限度地提高肺炎球菌疫苗的功效

• 批准号: MR/T016434/1
• 负责人: Nicholas Croucher
• 金额: $ 71.13万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT016434%2F1
• 关键词: Integrating; genomic; surveillance; ecological; modelling; Integrating; genomic; surveillance; ecological; modelling

Streptococcus pneumoniae, or the pneumococcus, is a bacterium found harmlessly living inside the noses of around half of young children in the UK. When they reach other parts of the body, pneumococci can cause harmful infections such as pneumonia, sepsis or meningitis. This is largely attributable to these bacteria having a capsule that protects them from the immune system. In 2010, the UK introduced a vaccine (called PCV13) that protected against 13 of the approximately 100 known capsule types. This eliminated most of these 13 capsule types from both disease and harmless carriage in infants. However, S. pneumoniae strains not affected by the vaccine increased in number to replace the lost capsule types. These strains did not cause disease in infants so frequently, and therefore PCV13 has reduced the amount of childhood pneumococcal disease. However, the replacing strains appear to be more likely to cause disease in adults, who catch the bacteria from healthy children. Hence the amount of adult pneumococcal disease has gone up since PCV13.Public Health England (PHE) lead the evaluation of PCV13 in the UK, and their surveillance of pneumococcal disease means they have the largest collection of well-characterised S. pneumoniae bacteria in the world. This project would select isolates from this collection to study using whole genome sequencing, to understand how the genetics of the bacterial population changed before and after vaccines (PCV13, and similar earlier versions) were introduced. New methods of DNA sequence analysis would be employed to merge UK data with that from research work around the world. These would enable the global migration patterns of S. pneumoniae strains to be traced, identifying the main origins of strains that have recently emerged in the UK.These genetic data will also enable mathematical modelling of the changes in circulating strains caused by PCV13. We have specific hypotheses about the genetics that underlies the changes after vaccination, but previously these have only been tested against bacteria collected from healthy children. This project will expand our models to incorporate the most harmful strains, which are rarely found in the nose. This is critical for understanding why PCV13 had effects on adult disease in the UK that were not common in other countries. This project will also test how accurately these models forecast ongoing trends in S. pneumoniae disease as new surveillance data are collected by PHE. This will help predict whether trends in the overall level of disease are likely to change in the next few years.We would make the model easily accessible to other scientists, such that they could improve and update it. By continually improving the model, we hope to use it as a tool for identifying the risks associated with each of the next generation of vaccines against S. pneumoniae, which are currently being developed. This would help ensure the UK made the right choice to avoid unintended consequences, as occurred with PCV13, and minimise the national burden of S. pneumoniae disease in both infants and adults. Scientists involved in the project serve on UK and international bodies that advise on the use of these vaccines, and therefore our results will be communicated to relevant agencies around the world. We will also explore whether our models and methods could be helpful in analysing other bacteria, particularly focusing on those for which new vaccines are being developed.

肺炎链球菌或肺炎球菌是一种细菌，发现在英国大约一半的幼儿中无害地生活在鼻子内。当它们到达身体的其他部位时，肺炎球菌会引起有害感染，例如肺炎，败血症或脑膜炎。这在很大程度上归因于这些细菌具有可保护它们免受免疫系统的胶囊。 2010年，英国引入了一种疫苗（称为PCV13），该疫苗可抵抗大约100种已知胶囊类型中的13种。这消除了婴儿中的这13种胶囊类型中的大多数。但是，不受疫苗影响的肺炎链球菌菌株数量增加，以替代丢失的胶囊类型。这些菌株不会如此频繁地引起婴儿疾病，因此PCV13减少了儿童肺炎球菌疾病的量。但是，替换菌株似乎更有可能引起成人疾病，他们从健康的儿童中捕获细菌。因此，自PCV13。英格兰公共卫生（PHE）领导英国PCV13的评估以来，成年肺炎球菌病的数量增加了，并且对肺炎球菌病的监测意味着他们拥有最大的碳化链球菌的肺炎链球菌细菌。该项目将从该集合中选择分离物，以使用整个基因组测序进行研究，以了解细菌种群的遗传学在疫苗之前和之后如何更改（PCV13和类似的早期版本）。将采用新的DNA序列分析方法将英国数据与世界各地的研究工作合并。这些将使肺炎链球菌菌株的全球迁移模式被追溯，确定最近在英国出现的菌株的主要起源。这些遗传数据还将实现由PCV13引起的循环菌株变化的数学建模。我们对疫苗接种后发生变化的遗传学有特定的假设，但以前仅对从健康儿童收集的细菌进行了测试。该项目将扩大我们的模型，以结合最有害的菌株，这些菌株在鼻子中很少发现。这对于理解为什么PCV13会对英国不常见的成人疾病产生影响至关重要。该项目还将测试这些模型预测肺炎链球菌疾病的持续趋势的准确程度，因为PHE收集了新的监视数据。这将有助于预测未来几年疾病总体水平的趋势是否可能发生变化。我们将使其他科学家可以轻松访问该模型，从而可以改善和更新。通过不断改进该模型，我们希望将其用作确定与目前正在开发的肺炎链球菌的下一代疫苗相关的风险。这将有助于确保英国做出正确的选择，以避免PCV13发生的意外后果，并最大程度地减少婴儿和成人肺炎链球菌疾病的全国负担。参与该项目的科学家在英国和国际机构提供有关使用这些疫苗的建议，因此我们的结果将与世界各地的相关机构传达。我们还将探讨我们的模型和方法是否有助于分析其他细菌，尤其是专注于开发新疫苗的细菌。