A qualitatively validated mathematical-computational model of the immune response to the yellow fever vaccine

Abstract

BackgroundAlthough a safe and effective yellow fever vaccine was developed more than 80 years ago, several issues regarding its use remain unclear. For example, what is the minimum dose that can provide immunity against the disease? A useful tool that can help researchers answer this and other related questions is a computational simulator that implements a mathematical model describing the human immune response to vaccination against yellow fever.MethodsThis work uses a system of ten ordinary differential equations to represent a few important populations in the response process generated by the body after vaccination. The main populations include viruses, APCs, CD8+ T cells, short-lived and long-lived plasma cells, B cells and antibodies.ResultsIn order to qualitatively validate our model, four experiments were carried out, and their computational results were compared to experimental data obtained from the literature. The four experiments were: a) simulation of a scenario in which an individual was vaccinated against yellow fever for the first time; b) simulation of a booster dose ten years after the first dose; c) simulation of the immune response to the yellow fever vaccine in individuals with different levels of naïve CD8+ T cells; and d) simulation of the immune response to distinct doses of the yellow fever vaccine.ConclusionsThis work shows that the simulator was able to qualitatively reproduce some of the experimental results reported in the literature, such as the amount of antibodies and viremia throughout time, as well as to reproduce other behaviors of the immune response reported in the literature, such as those that occur after a booster dose of the vaccine.

Validation of a yellow fever vaccine model using data from primary vaccination in children and adults, re-vaccination and dose-response in adults and studies with immunocompromised individuals

“…The model used in this work consists of a system of ordinary differential equations (ODEs), which were originally proposed in a previous work [ 1 , 17 ], and reproduced here. These equations represent the main populations involved in the immune response to the vaccination, as well as the virus itself.…”

“…One of the main changes made in our previous work [ 1 ], after access to experimental data, was to adjust the units used in the model. The amount of vaccine virus used as the model’s initial condition was one of these changes.…”

“…The amount of vaccine virus used as the model’s initial condition was one of these changes. Previously [ 1 ], the value 27,476 IU was used, which is the average amount of virus present in the full dose, that is, in 0.5 mL. Variations in the amount of virus across vaccine lots were not considered.…”

“…Although YFV is considered safe, there are rare but serious adverse effects that need to be reassessed, such as viscerotropic and neurotropic events [ 1 ]. There are also questions regarding the safety of vaccinating specific populations such as the elderly, people living with Human Immunodeficiency Virus (HIV)/AIDS, and other immunocompromised populations.…”

“…With mathematical and computational models, it is possible to evaluate in silico different scenarios related to vaccination and answer important questions which remain open, such as the minimal dose that confers immunity and immunity duration. The idea of using computer tools during the clinical development stage was then applied to model the immune response to the YFV [ 1 , 16 ]. Results showed that mathematical models could capture the immune response to the YFV, and in subsequent work the model was validated quantitatively [ 17 ]…”