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Computational modeling of the immune responses induced by both natural HPV infections and vaccination with Gardasil®

Gustavo Olivera-Botello 1
1 Evaluation et modélisation des effets thérapeutiques
Département biostatistiques et modélisation pour la santé et l'environnement [LBBE]
Abstract : Two prophylactic vaccines have demonstrated to prevent infections with the human papillomavirus (HPV). Thus, they have been in the market for the last four years, or so. The three main objectives of the present project were: i) to study in-silico the immunogenicity of one of these vaccines (Gardasil®); ii) to study in-silico the natural history of an HPV infection, and iii) to assess in-silico the potential of the following therapeutic hypothesis : the intramuscular administration of Gardasil® to patients already suffering from a recurrent respiratory papillomatosis would result in a better prognosis thanks to the fact that the HPV-specific immunoglobulins that would bathe the affected tissue would impede the virus to complete its life cycle and, therefore, the disease to progress. The main conclusions are: i) according to our simulations, the minimum serum IgG titer required for hampering the progression of a recurrent respiratory papillomatosis would be 200 mMU/mL ; ii) in order to keep, within a time window of ten years, the anti-HPV IgG titer over the just-mentioned therapeutic-effect threshold, the biggest possible fraction of time and through the administration of the smallest possible number of booster doses, it would be necessary, according to our simulations, to adopt the following vaccination schedule: the basic three doses (at months 0, 2 and 6), followed by three successive booster doses, every six months, until reaching the 24th month, followed by a late final booster dose, 18 months later. iii) incidentally, it would seem to be inappropriate, according to our simulations, to modify the original initial vaccination schedule (at months 0, 2 and 6)
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Gustavo Olivera-Botello. Computational modeling of the immune responses induced by both natural HPV infections and vaccination with Gardasil®. Human health and pathology. Université Claude Bernard - Lyon I, 2011. English. ⟨NNT : 2011LYO10038⟩. ⟨tel-00846182⟩

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