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: 8708910
• 负责人: Andrew F. Read
• 金额: $ 24.3万
• 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 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8708910
• 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; Relative (related person); Resistance; Risk; Science; System; Vaccinated; Vaccination; Vaccines; Virulence; Virulent; Virus; Work; anthropogenesis; environmental change; epidemiological model; experience; field study; fitness; genetic vaccine; killings; mathematical model; next generation; novel vaccines; offspring; operation; pathogen; research study; response; theories; transmission process

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（和关键的数学模型之一）