Within-host mathematical models to study antibody kinetics after the prophylactic Ebola vaccine in the Democratic Republic of the Congo

Abstract

Ebola virus disease remains a threat in different Sub-Saharan African countries more particularly in the Democratic Republic of Congo, where persistent outbreaks are driven by human populations living in close proximity to animal reservoirs. While vaccines like Ad26.ZEBOV and MVA-BN-Filo are safe and immunogenic, the dynamics of antibody responses after the two-dose regimen and booster vaccination are not fully understood. Within-host mathematical models offer valuable insights into disease dynamics and waning immunity, but datadriven mechanistic models of antibody kinetics remain scarce. The present study seeks to elucidate the processes involved in antibody kinetics after the two-dose vaccine regimen with Ad26.ZEBOV and MVA-BN-Filo vaccines, followed by a booster dose vaccination with Ad26. ZEBOV, addressing challenges in inference for and implementation of within-host approaches. By integrating established theoretical frameworks with recent empirical findings on antibody kinetics following Ebola vaccination, we illustrate how mechanistic modeling can enhance and refine our understanding of antibody dynamics. Specifically, we emphasize the distinction in the half-life of antibody responses at different vaccination time points and explore the role of vaccine antigens in eliciting an immunological response through the formation and activation of germinal center mediated response. Careful consideration was given to the development of a model that is both interpretable and practically feasible. The half-life of the antibody response was found to be longer after booster vaccination compared to after the second vaccine dose, indicating a steadier decay process. This may be due to the improved quality of antibodies generated, the formation of memory B cells sustaining antibody production, and antigen-antibody binding. This study highlights critical considerations for implementing within-host mechanistic models and the need for robust data to accurately estimate model parameters. Further research is essential to elucidate the decay dynamics of memory B cells and long-lived plasma cells, as these processes play a pivotal role in sustaining antibody-mediated immunity.