Sequential infections with different dengue serotypes (DENV-1, 4) significantly increase the risk of a severe disease outcome (fever, shock, and hemorrhagic disorders). Two hypotheses have been proposed to explain the severity of the disease: (1) antibody-dependent enhancement (ADE) and (2) original T cell antigenic sin. In this work, we explored the first hypothesis through mathematical modeling. The proposed model reproduces the dynamic of susceptible and infected target cells and dengue virus in scenarios of infection-neutralizing and infection-enhancing antibody competition induced by two distinct serotypes of the dengue virus during secondary infection. The enhancement and neutralization functions are derived from basic concepts of chemical reactions and used to mimic binding to the virus by two distinct populations of antibodies. The analytic study of the model showed the existence of two equilibriums: a disease-free equilibrium and an endemic one. Using the concept of the basic reproduction number \({\mathcal {R}}_0\), we performed the asymptotic stability analysis for the two equilibriums. To measure the severity of the disease, we considered the maximum value of infected cells as well as the time when this maximum is reached. We observed that it corresponds to the time when the maximum enhancing activity for the infection occurs. This critical time was calculated from the model to be a few days after the occurrence of the infection, which corresponds to what is observed in the literature. Finally, using as output \({\mathcal {R}}_0\), we were able to rank the contribution of each parameter of the model. In particular, we highlighted that the cross-reactive antibody responses may be responsible for the disease enhancement during secondary heterologous dengue infection.

不同登革热血清型（DENV-1、4）的连续感染显着增加了严重疾病结果（发烧、休克和出血性疾病）的风险。已提出两种假设来解释该疾病的严重程度：(1) 抗体依赖性增强 (ADE) 和 (2) 原始 T 细胞抗原罪。在这项工作中，我们通过数学建模探索了第一个假设。所提出的模型再现了在二次感染期间由两种不同血清型登革热病毒诱导的感染中和和感染增强抗体竞争的情况下易感和感染的靶细胞和登革热病毒的动态。增强和中和功能源自化学反应的基本概念，用于模拟两种不同抗体群与病毒的结合。该模型的分析研究表明存在两个平衡：无病平衡和地方病平衡。使用概念基本再生数 \({\mathcal {R}}_0\)，我们对两个平衡进行了渐近稳定性分析。为了衡量疾病的严重程度，我们考虑了受感染细胞的最大值以及达到该最大值的时间。我们观察到它对应于感染的最大增强活性发生的时间。这个关键时间是根据模型计算出的感染发生后的几天，这与文献中观察到的情况相对应。最后，使用作为输出\({\mathcal {R}}_0\)，我们能够对模型的每个参数的贡献进行排名。特别是，我们强调交叉反应性抗体反应可能是继发性异源登革热感染期间疾病加重的原因。