Vaccines as drivers of disease emergence: transmission ecology and virulence evol

疫苗作为疾病出现的驱动因素：传播生态学和毒力进化

• 批准号: 9115200
• 负责人: Andrew F. Read
• 金额: $ 23.72万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-28 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115200
• 关键词: Animal Diseases; Animals; Avian Influenza; Biology; Birds; Blood Circulation; Case Study; Cessation of life; Clinical Trials; Communicable Diseases; Data; Disease; Domestic Fowls; Ecology; Elements; Epidemiology; Evolution; Farming environment; Future; Health; Human; Hygiene; Immunity; Immunization; Industry; Instruction; Investigation; Livestock; Marek Disease; Maternal antibody; Measurement; Measures; Modeling; Natural Selections; Population; Risk; Science; System; Vaccinated; Vaccination; Vaccines; Virulence; Virulent; Virus; Work; anthropogenesis; environmental change; epidemiological model; experience; field study; fitness; genetic resistance; killings; mathematical model; next generation; novel vaccines; offspring; operation; pathogen; research study; response; theories; transmission process; viral transmission

Why are pathogens not more virulent? Conventional wisdom (and one of the key mathematical models in the ecological and evolutionary theory of infectious diseases) is that evolution removes excessively lethal Strains. Pathogens that kill their hosts too rapidly shorten their own infectious periods and hence have lower evolutionary fitness than less lethal strains. If so, what happens when vaccines protect hosts from death? Gould immunization enable the circulation of strains that would once have been removed by natural selection? That would increase the net virulence of pathogen population experienced by unvaccinated hosts. The 'evolutionary risk' of public and animal health measures cannot be directly assessed in clinical trials because pathogen evolution will be seen only after population-wide implementation. We have recently shown experimentally that vaccination does indeed make possible the onward transmission of hyperpathogenic strains of Marek's disease virus (MDV) in poultry. We seek to now to dissect the effects of immunization on the ecology of transmission in this farm animal system, so as to evaluate the impact of contemporary and next generation vaccines on the future evolution of this disease. We will fuse experimental measurements of virus transmission from vaccinated and unvaccinated birds, field investigations of farm epidemiology and mathematical evolutionary-epidemiological models. Our primary objective is to dissect the selective forces imposed by immunization and other management pratices on MDV virulence, and to evaluate their evolutionary and epidemiological consequences. This will make it possible to use evolutionary epidemiological models to analyze evolutionary trajectories and to assess the evolutionary consequences of contrasting management strategies on the evolution of MDV and other pathogens. The biology and ecological context of MDV offer unprecedented scientific opportunities. We aim to make MDV a canonical case study of pathogen adaptation and disease emergence in response to human-induced environmental change.

为什么病原体没有更强的毒性？传统的智慧（和一个关键的数学模型， 传染病的生态和进化理论）是进化消除了过度致命的 菌株过快杀死宿主的病原体缩短了它们自己的感染期， 进化适应性比低致命性菌株强。如果是这样，当疫苗保护宿主免于死亡时会发生什么？ 古尔德免疫使那些曾经被自然消除的菌株得以传播。 选择？这将增加未接种疫苗的宿主所经历的病原体群体的净毒力。 公共和动物健康措施的“进化风险”无法在临床试验中直接评估 因为只有在整个人群实施之后才能看到病原体的演变。我们最近 实验表明，接种疫苗确实有可能进一步传播 鸡马立克氏病病毒（MDV）高致病性毒株。我们现在试图剖析 免疫对该农场动物系统中传播生态学的影响，以评估 当代和下一代疫苗对这种疾病的未来演变的影响。 我们将融合接种疫苗和未接种疫苗的鸟类的病毒传播实验测量， 农场流行病学的实地调查和数学进化流行病学模型。我们的首要 目标是剖析免疫和其他管理实践对MDV施加的选择性力量 毒力，并评估其进化和流行病学后果。这将使得可以 使用进化流行病学模型来分析进化轨迹，并评估进化 对比管理策略对MDV和其他病原体进化的影响。的 MDV的生物学和生态学背景提供了前所未有的科学机会。我们的目标是使MDV成为 病原体适应和疾病出现的典型案例研究 环境变化

项目成果

Industry-Wide Surveillance of Marek's Disease Virus on Commercial Poultry Farms.

• DOI: 10.1637/11525-110216-reg.1
• 发表时间: 2017-06
• 期刊: Avian diseases
• 影响因子: 1.4
• 作者: Kennedy DA;Cairns C;Jones MJ;Bell AS;Salathé RM;Baigent SJ;Nair VK;Dunn PA;Read AF
• 通讯作者: Read AF

Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens.

• DOI: 10.1371/journal.pbio.1002198
• 发表时间: 2015-07
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Read AF;Baigent SJ;Powers C;Kgosana LB;Blackwell L;Smith LP;Kennedy DA;Walkden-Brown SW;Nair VK
• 通讯作者: Nair VK