Sebayang Afrina Andriani, Fahlena Hilda, Anam Vizda, Knopoff Damián, Stollenwerk Nico, Aguiar Maíra, Soewono Edy
Department of Mathematics, Institut Teknologi Bandung, Bandung 40132, Indonesia.
Basque Centre for Applied Mathematics (BCAM), Alameda Mazarredo, 14, 48009 Bilbao, Spain.
Biology (Basel). 2021 Sep 20;10(9):941. doi: 10.3390/biology10090941.
Dengue fever is a viral mosquito-borne infection and a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called antibody-dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: (i) primary dengue infection, (ii) secondary dengue infection with the same (homologous) dengue virus and (iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights into the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.
登革热是一种由蚊子传播的病毒性感染疾病，也是国际公共卫生领域的重大关切。全球有25亿人面临感染风险，疾病的严重程度受个体在自然感染前的免疫状态（血清阴性或血清阳性）影响。登革热由四种抗原相关但不同的血清型（DENV-1至DENV-4）引起，感染一种血清型可使人对该血清型产生终身免疫，并对其他血清型产生一段时间的临时交叉免疫（TCI）。接触第二种血清型时的临床反应较为复杂，存在所谓的抗体依赖性增强（ADE）过程，即先前登革热感染产生的抗体不能中和反而增强新感染的疾病加重现象，这一过程被用于解释重症疾病的病因。在本文中，我们提出了一个简约的数学模型框架，用于定性描述由抗体介导的登革热免疫反应。分析并比较了三种模型：（i）初次登革热感染，（ii）感染相同（同源）登革热病毒的二次登革热感染，以及（iii）感染不同（异源）登革热病毒的二次登革热感染。我们探究了病毒复制、抗体产生和感染清除随时间的变化特征。该模型基于体细胞与游离病毒的相互作用构建，感染细胞会激活抗体产生。我们的数学结果在定性上与经验免疫学文献中描述的结果相似，为重症疾病的免疫发病机制提供了见解。本文呈现的结果有助于未来评估登革热疫苗影响的研究方向。
