Modeling the Relationship Between Antibody-Dependent Enhancement and Disease Severity in Secondary Dengue Infection

Author(s)

Camargo, Felipe de A. ^[1] ; Adimy, Mostafa ^[2] ; Esteva, Lourdes ^[3] ; Metayer, Clemence ^[2] ; Ferreira, Claudia P. ^[1]

Affiliation

^[1] Sao Paulo State Univ, UNESP, Inst Biosci, BR-18618689 Botucatu, SP - Brazil

^[2] Univ Lyon 1, Univ Lyon, Inst Camille Jordan, INRIA, 43 Bd 11 Novembre 1918, F-69200 Villeurbanne - France

^[3] Univ Nacl Autonoma Mexico, Fac Ciencias, Dept Matemat, Mexico City 04510, DF - Mexico

• Document type: Journal article
• Source: Bulletin of Mathematical Biology; v. 83, n. 8 AUG 2021.
• Web of Science Citations: 0

Abstract

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 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 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. (AU)

• FAPESP's process: 19/22157-5 - Modelling and biological control of vector-borne diseases: the case of Malaria and Dengue
• Grantee: Cláudia Pio Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/23202-4 - Modelling the dengue hemorrhagic fever
• Grantee: Cláudia Pio Ferreira
• Support Opportunities: Research Grants - Visiting Researcher Grant - International