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Modélisation et optimisation de la réponse à des vaccins et à des interventions immunothérapeutiques : application au virus Ebola et au VIH

Abstract : Vaccines have been one of the most successful developments in public health in the last years. However, a major challenge still resides in developing effective vaccines against infectious diseases such as HIV or Ebola virus. This can be attributed to our lack of deep knowledge in immunology and the mode of action of immune memory. Mathematical models can help understanding the mechanisms of the immune response, quantifying the underlying biological processes and eventually developing vaccines based on a solid rationale. First, we present a mechanistic model for the dynamics of the humoral immune response following Ebola vaccine immunizations based on ordinary differential equations. The parameters of the model are estimated by likelihood maximization in a population approach, which allows to quantify the process of the immune response and its factors of variability. In particular, the vaccine regimen is found to impact only the response on a short term, while significant differences between subjects of different geographic locations are found at a longer term. This could have implications in the design of future clinical trials. Then, we develop a numerical tool based on dynamic programming for optimizing schedule of repeated injections. In particular, we focus on HIV-infected patients under treatment but unable to recover their immune system. Repeated injections of an immunotherapeutic product (IL-7) are considered for improving the health of these patients. The process is first by a piecewise deterministic Markov model and recent results of the impulse control theory allow to solve the problem numerically with an iterative sequence. We show in a proof-of-concept that this method can be applied to a number of pseudo-patients. All together, these results are part of an effort to develop sophisticated methods for analyzing data from clinical trials to answer concrete clinical questions.
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https://tel.archives-ouvertes.fr/tel-02343175
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Submitted on : Saturday, November 2, 2019 - 1:03:55 AM
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Chloé Pasin. Modélisation et optimisation de la réponse à des vaccins et à des interventions immunothérapeutiques : application au virus Ebola et au VIH. Médecine humaine et pathologie. Université de Bordeaux, 2018. Français. ⟨NNT : 2018BORD0208⟩. ⟨tel-02343175⟩

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