Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine.
Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine.
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DOI：
10.1073/pnas.2216667120
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发表时间：
2023-03-14
影响因子：
11.1
通讯作者：
Streicker, Daniel G.
中科院分区：
文献类型：
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作者：
Griffiths, Megan E.;Meza, Diana K.;Haydon, Daniel T.;Streicker, Daniel G.
野生动物病毒的蔓延造成全球健康和经济负担，并且在很大程度上仍然无法预防。破坏野生动物宿主内病毒传播的疫苗可能会防止病毒外溢，但面临着向偏远和隐居的野生动物种群提供疫苗这一尚未解决的挑战。利用良性病毒作为自传播疫苗提供了一种可能的解决方案。在吸血蝙蝠中发现的β疱疹病毒是针对吸血蝙蝠狂犬病的传播疫苗的潜在候选载体，吸血蝙蝠狂犬病是拉丁美洲狂犬病的重要来源，但其在自然蝙蝠种群中的传播动态仍不清楚。使用流行病学模型和现场衍生的病毒基因组数据，我们模拟了未来基于乙型疱疹病毒的疫苗可能如何传播。我们展示了其高疫苗覆盖率和长期预防狂犬病爆发的能力。传染性疫苗是一种新兴的生物技术，有望消除野生动物种群中的病原体。此类疫苗将对天然存在的非病原性病毒（“病毒载体”）进行基因改造，以表达病原体抗原，同时保留其传播能力。众所周知，目标野生动物种群内候选病毒载体的流行病学问题很难解决，但它支持在疫苗开发进行重大投资之前选择有效载体。在这里，我们使用时空复制深度测序来参数化 Desmodus rotundus betaherpesvirus (DrBHV) 的竞争流行病学机制模型，DrBHV 是一种针对吸血蝙蝠传播的狂犬病的传播疫苗的拟议载体。使用 6 年多收集的 36 个病毒株和特定地点的流行时间序列，我们发现具有潜伏期和重新激活周期的终生感染，加上高 R0（6.9；CI：4.39 至 7.85），对于解释在野生蝙蝠中观察到的 DrBHV 感染模式是必要的。这些流行病学特性表明，DrBHV 可能适合作为终身、自我增强和可传播的疫苗的载体。模拟显示，用 DrBHV 载体的狂犬病疫苗接种单只蝙蝠可以使超过 80% 的蝙蝠种群免疫，从而将狂犬病爆发的规模、频率和持续时间减少 50% 至 95%。预计已接种疫苗的个体的传染性疫苗会逐渐丧失，但可以通过接种更大但实际上可实现比例的蝙蝠种群来应对。使用可访问的基因组数据对流行病学模型进行参数化，使传染性疫苗距离实施又近了一步。
Spillover of wildlife viruses causes global health and economic burdens and remains largely unpreventable. Vaccines that disrupt virus transmission within wildlife reservoirs might prevent spillover but face the unresolved challenge of delivering vaccines to remote and reclusive wildlife populations. Exploiting benign viruses as self-spreading vaccines offers a possible solution. A betaherpesvirus found in vampire bats is a potential candidate vector for a transmissible vaccine targeting vampire bat rabies, an important source of rabies in Latin America, but the dynamics of its transmission in natural bat populations remain unknown. Using epidemiological models and field-derived viral genomic data, we simulate how a future betaherpesvirus-based vaccine might spread. We demonstrate its capacity for high vaccine coverage and long-term prevention of rabies outbreaks. Transmissible vaccines are an emerging biotechnology that hold prospects to eliminate pathogens from wildlife populations. Such vaccines would genetically modify naturally occurring, nonpathogenic viruses (“viral vectors”) to express pathogen antigens while retaining their capacity to transmit. The epidemiology of candidate viral vectors within the target wildlife population has been notoriously challenging to resolve but underpins the selection of effective vectors prior to major investments in vaccine development. Here, we used spatiotemporally replicated deep sequencing to parameterize competing epidemiological mechanistic models of Desmodus rotundus betaherpesvirus (DrBHV), a proposed vector for a transmissible vaccine targeting vampire bat-transmitted rabies. Using 36 strain- and location-specific time series of prevalence collected over 6 y, we found that lifelong infections with cycles of latency and reactivation, combined with a high R0 (6.9; CI: 4.39 to 7.85), are necessary to explain patterns of DrBHV infection observed in wild bats. These epidemiological properties suggest that DrBHV may be suited to vector a lifelong, self-boosting, and transmissible vaccine. Simulations showed that inoculating a single bat with a DrBHV-vectored rabies vaccine could immunize >80% of a bat population, reducing the size, frequency, and duration of rabies outbreaks by 50 to 95%. Gradual loss of infectious vaccine from vaccinated individuals is expected but can be countered by inoculating larger but practically achievable proportions of bat populations. Parameterizing epidemiological models using accessible genomic data brings transmissible vaccines one step closer to implementation.
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影响因子：
--
作者：
Gupta P;Singh MP;Goyal K;Tripti P;Ansari MI;Obli Rajendran V;Dhama K;Malik YS
通讯作者：
Malik YS
影响因子：
4.4
作者：
Cao, Yang;Gillespie, Daniel T.;Petzold, Linda R.
通讯作者：
Petzold, Linda R.
通过复制能力控制的疱疹病毒载体进行免疫。
影响因子：
5.4
作者：
Bloom DC;Tran RK;Feller J;Voellmy R
通讯作者：
Voellmy R
影响因子：
4.5
作者：
Grinde B
通讯作者：
Grinde B
影响因子：
17.1
作者：
Hansen, Scott G.;Marshall, Emily E.;Picker, Louis J.
通讯作者：
Picker, Louis J.