Virus antibody dynamics in primary and secondary dengue infections

Abstract

Dengue viral infections show unique infection patterns arising from its four serotypes, 2,3,4). Its effects range from simple fever in primary infections to potentially fatal secondary infections. We analytically and numerically analyse virus dynamics and humoral response in a host during primary and secondary dengue infection for long periods using micro-epidemic models. The models presented here incorporate time delays, antibody dependent enhancement (ADE), a dynamic switch and a correlation factor between different DENV serotypes. We find that the viral load goes down to undetectable levels within 7-14 days as is observed for dengue infection, in both cases. For primary infection, the stability analysis of steady states shows interesting dependence on the time delay involved in the production of antibodies from plasma cells. We demonstrate the existence of a critical value for the immune response parameter, beyond which the infection gets completely cured. For secondary infections with a different serotype, the homologous antibody production is enhanced due to the influence of heterologous antibodies. The antibody production is also controlled by the correlation factor, which is a measure of similarities between the different DENV serotypes involved. Our results agree with clinically observed humoral responses for primary and secondary infections.

Challenges in dengue research: A computational perspective

“…The vast majority of dengue models has focused on viral dynamics at the population‐level. Given the importance that the within‐host processes (e.g., ADE and cross‐immunity) play for both viral transmission and disease pathology, it is thus surprising that just over a handful of studies have so far investigated viral dynamics at the within‐host level (Nuraini, Tasman, Soewono, & Sidarto, ; Ansari & Hesaaraki, ; Clapham, Tricou, N. V., Simmons, & Ferguson, ; Ben‐Shachar & Koelle, ; Gujarati & Ambika, ; Nikin‐Beers & Ciupe, ; Clapham, Quyen, Kien, Dorigatti, & Simmons, ; Ben‐Shachar, Schmidler, & Koelle, ). This could, however, be explained by the little understanding we currently have about the interactions between the virus, its target cells and the host immune responses that eventually clear infection, which may also be directly responsible for clinical outcome.…”

“…() focused on the distinction between these two mechanisms and found that either could explain the data (viral and antibody titres) equally well. Two other studies have focused on the general mechanics of humoral responses (B cell and free antibody) using different modelling frameworks (Gujarati & Ambika, ; Nikin‐Beers & Ciupe, ). While one study concluded that enhancing antibodies (ADE) were key in secondary infections (Gujarati & Ambika, ), the other study suggested instead a direct decrease of overall heterologous viral clearance, whereby cross‐reactive antibodies render virions unavailable for further binding and subsequent clearance by ADCC (Nikin‐Beers & Ciupe, ).…”

“…Two other studies have focused on the general mechanics of humoral responses (B cell and free antibody) using different modelling frameworks (Gujarati & Ambika, ; Nikin‐Beers & Ciupe, ). While one study concluded that enhancing antibodies (ADE) were key in secondary infections (Gujarati & Ambika, ), the other study suggested instead a direct decrease of overall heterologous viral clearance, whereby cross‐reactive antibodies render virions unavailable for further binding and subsequent clearance by ADCC (Nikin‐Beers & Ciupe, ). In another study, the question about the role of the adaptive and innate immune responses in disease severity was addressed (Ben‐Shachar & Koelle, ; Ben‐Shachar et al., ).…”

“…In some cases, the models and the data sets differed, making it hard to assess whether contrasting conclusions are data‐ or model‐driven. For instance, some models propose a key role of innate immunity in clearance of primary infection (Ben‐Shachar & Koelle, ; Ben‐Shachar et al., ), while others propose that either humoral or cell‐mediated clearance is required (Nuraini et al., ; Ansari & Hesaaraki, ; Clapham et al., ; Gujarati & Ambika, ; Nikin‐Beers & Ciupe, ; Clapham et al., ). Equally, asymmetries between serotypes in both cell infectivity and timing of peak viraemia versus symptomatic manifestations were reported in one study (Ben‐Shachar et al., ) but not in another (Clapham et al., ).…”

A generalized within-host model of dengue infection with a non-constant monocyte production rate

“…There have been many mathematical studies of dengue infection. Of those, relatively few references [3,8,9,12,[16][17][18][19]21] are concerned with within-host dynamics. In all of these, it is assumed that the production of target cells (monocytes) is constant.…”