Pan-Ngum Wirichada, Kinyanjui Timothy, Kiti Moses, Taylor Sylvia, Toussaint Jean-François, Saralamba Sompob, Van Effelterre Thierry, Nokes D James, White Lisa J
Mathematical and Economics Modelling (MAEMOD) Research Group, Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
School of Mathematics, Alan Turing Building, University of Manchester, Oxford Road, Manchester, UK; KEMRI-Wellcome Trust Research Programme, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.
Vaccine. 2017 Jan 5;35(2):403-409. doi: 10.1016/j.vaccine.2016.10.073. Epub 2016 Nov 30.
Respiratory syncytial virus (RSV) is the major viral cause of infant and childhood lower respiratory tract disease worldwide. Defining the optimal target product profile (TPP) is complicated due to a wide range of possible vaccine properties, modalities and an incomplete understanding of the mechanism of natural immunity. We report consensus population level impact projections based on two mathematical models applied to a low income setting.
Two structurally distinct age-specific deterministic compartmental models reflecting uncertainty associated with the natural history of infection and the mechanism by which immunity is acquired and lost were constructed. A wide range of vaccine TPPs were explored including dosing regime and uptake, and effects in the vaccinated individual on infectiousness, susceptibility, duration of protection, disease severity and interaction with maternal antibodies and natural induced immunity. These were combined with a range of vaccine implementation strategies, targeting the highest priority age group and calibrated using hospitalization data from Kilifi County Hospital, Kenya.
Both models were able to reproduce the data. The impact predicted by the two models was qualitatively similar across the range of TPPs, although one model consistently predicted higher impact than the other. For a proposed realistic range of scenarios of TPP combinations, the models predicted up to 70% reduction in hospitalizations in children under five years old. Vaccine designs which reduced the duration and infectiousness of infection were predicted to have higher impacts. The models were sensitive to the coverage and rate of loss of vaccine protection but not to the interaction between vaccine and maternal/naturally acquired immunity.
The results suggest that vaccine properties leading to reduced virus circulation by lessening the duration and infectiousness of infection upon challenge are of major importance in population RSV disease control. These features should be a focus for vaccine development.
呼吸道合胞病毒（RSV）是全球婴幼儿下呼吸道疾病的主要病毒病因。由于疫苗可能具有多种特性、形式，且对自然免疫机制的理解尚不完整，因此确定最佳目标产品特性（TPP）较为复杂。我们报告了基于两种数学模型应用于低收入环境的共识性人群水平影响预测。
构建了两个结构不同的年龄特异性确定性 compartmental 模型，反映与感染自然史以及免疫获得和丧失机制相关的不确定性。探索了多种疫苗 TPP，包括给药方案和接种率，以及疫苗对个体传染性、易感性、保护持续时间、疾病严重程度的影响，以及与母体抗体和自然诱导免疫的相互作用。将这些与一系列疫苗实施策略相结合，针对最高优先级年龄组，并使用肯尼亚基利菲县医院的住院数据进行校准。
两个模型均能够重现数据。尽管一个模型始终预测的影响高于另一个模型，但在一系列 TPP 中，两个模型预测的影响在质量上相似。对于一系列拟议的 TPP 组合实际情景，模型预测五岁以下儿童住院率最多可降低 70%。预计可缩短感染持续时间和传染性的疫苗设计将产生更高的影响。模型对疫苗保护的覆盖率和丧失率敏感，但对疫苗与母体/自然获得免疫之间的相互作用不敏感。
结果表明，通过缩短感染持续时间和传染性来减少病毒传播的疫苗特性在人群 RSV 疾病控制中至关重要。这些特性应成为疫苗开发的重点。
