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

Abstract

Background

An effective yellow fever (YF) vaccine has been available since 1937. Nevertheless, questions regarding its use remain poorly understood, such as the ideal dose to confer immunity against the disease, the need for a booster dose, the optimal immunisation schedule for immunocompetent, immunosuppressed, and pediatric populations, among other issues. This work aims to demonstrate that computational tools can be used to simulate different scenarios regarding YF vaccination and the immune response of individuals to this vaccine, thus assisting the response of some of these open questions.

Results

This work presents the computational results obtained by a mathematical model of the human immune response to vaccination against YF. Five scenarios were simulated: primovaccination in adults and children, booster dose in adult individuals, vaccination of individuals with autoimmune diseases under immunomodulatory therapy, and the immune response to different vaccine doses. Where data were available, the model was able to quantitatively replicate the levels of antibodies obtained experimentally. In addition, for those scenarios where data were not available, it was possible to qualitatively reproduce the immune response behaviours described in the literature.

Conclusions

Our simulations show that the minimum dose to confer immunity against YF is half of the reference dose. The results also suggest that immunological immaturity in children limits the induction and persistence of long-lived plasma cells are related to the antibody decay observed experimentally. Finally, the decay observed in the antibody level after ten years suggests that a booster dose is necessary to keep immunity against YF.