Modeling the Evolutionary and Public Health Impacts of HIV Adaptation in Response to Vaccination

模拟艾滋病毒适应对疫苗接种的进化和公共卫生影响

• 批准号: 9410707
• 负责人: Joshua T Herbeck
• 金额: $ 41.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9410707
• 关键词: Africa South of the Sahara; Behavioral; Complex; Computer software; Development; Enrollment; Epidemic; Epidemiology; Evolution; Gene Frequency; Genetic; Genetic Variation; Genotype; Goals; HIV; HIV Vaccine Trials Network; HIV vaccine; Heritability; Heterosexuals; Individual; Infection; Infection prevention; Investigation; Link; Methods; Modeling; Natural Selections; Online Systems; Outcome; Output; Phase; Phenotype; Philosophy; Placebos; Population; Prevention; Process; Public Health; Reproducibility; Reproduction; Risk; Schedule; Source; Study models; Vaccination; Vaccine Antigen; Vaccine Design; Vaccines; Variant; Viral; Work; base; experimental study; fitness; global health; improved; mathematical model; novel; open source; prevent; programs; repository; resistant strain; response; success; transmission process; trend; user-friendly; vaccine efficacy; vaccine response; vaccine trial

ABSTRACT Despite the existence of effective methods for prevention, HIV continues to be a global health crisis. The need for an HIV vaccine remains paramount. The phase III RV144 vaccine trial is the only trial of an HIV vaccine that showed modest success in preventing infection, with an estimated 31% vaccine efficacy at 3.5 years post- enrollment. However, vaccines can result in the emergence and spread of vaccine-resistant strains, via natural selection and strain replacement. The potential for such population-level adaptation in HIV has not been considered in HIV vaccine-related modeling studies. Our recent work in HIV evolutionary and epidemic modeling suggests that HIV may adapt rapidly in response to a partially effective vaccine similar to RV144. Our goal for this project is to predict the potential population-level impact of an HIV evolutionary response to vaccination. First, we will extend our existing HIV epidemic model (EvoNetHIV) to incorporate a broad set of vaccine-related parameters. Second, we will use this model to quantify outcomes of viral adaptation and predict public health impact across the set of vaccine-related parameters. We expect that incorporating a vaccine-specific evolutionary framework into our HIV epidemic model will substantially improve predictions related to the public health impact of HIV vaccination programs. We also expect that, due to our open source software philosophy, our evolutionary approach will be easily integrated into the epidemic models of other scientific groups.

抽象的 尽管存在有效的预防方法，但艾滋病毒仍然是全球健康危机。需要 对于HIV疫苗仍然是最重要的。 III期RV144疫苗试验是HIV疫苗的唯一试验 在预防感染方面表现出适度的成功，估计在3。5年后的3.5岁疫苗功效 注册。但是，疫苗可以通过自然导致抗疫苗抗性菌株的出现和传播 选择和应变替代。这种人群级适应艾滋病毒的潜力尚未 在HIV疫苗相关的建模研究中考虑。我们最近在艾滋病毒进化和流行病建模方面的工作 表明HIV可能会迅速适应类似于RV144的部分有效疫苗。我们的目标 该项目是为了预测HIV进化反应对疫苗接种的潜在人群水平的影响。 首先，我们将扩展现有的HIV流行模型（EVONETHIV），以结合一组与疫苗有关 参数。第二，我们将使用该模型来量化病毒适应的结果并预测公共卫生 在一组与疫苗相关的参数中的影响。我们预计合并特定于疫苗的 进化框架进入我们的艾滋病毒流行模型将大大改善与公众相关的预测 HIV疫苗接种计划的健康影响。我们还希望，由于我们的开源软件理念， 我们的进化方法将很容易地整合到其他科学群体的流行模型中。