Combining agent based-models and virtual screening techniques to predict the best citrus-derived vaccine adjuvants against human papilloma virus

结合基于代理的模型和虚拟筛选技术来预测针对人乳头瘤病毒的最佳柑橘衍生疫苗佐剂

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作者:Marzio Pennisi, Giulia Russo, Silvia Ravalli, Francesco Pappalardo

Background

Human papillomavirus infection is a global social burden that, every year, leads to thousands new diagnosis of cancer. The introduction of a protocol of immunization, with Gardasil and Cervarix vaccines, has radically changed the way this infection easily spreads among people. Even though vaccination is only preventive and not therapeutic, it is a strong tool capable to avoid the consequences that this pathogen could cause. Gardasil vaccine is not free from side effects and the duration of immunity is not always well determined. This work

Conclusions

We built up a computational infrastructure made by a virtual screening approach able to preselect promising citrus derived compounds, and by an agent based model that reproduces HPV dynamics subject to vaccine stimulation. This integrated methodology was able to predict the best protocol that confers a very good immune response against HPV infection. We finally tested the in silico results through in vivo experiments on mice, finding good agreement.

Results

With the aim to get a stronger immune response against Hpv infection we built an in silico model that delivers a way to predict the best adjuvants and the optimal means of administration to obtain such a goal. Simulations envisaged that the use of Neohesperidin elicited a strong immune response that was then validated in vivo. Conclusions: We built up a computational infrastructure made by a virtual screening approach able to preselect promising citrus derived compounds, and by an agent based model that reproduces HPV dynamics subject to vaccine stimulation. This integrated methodology was able to predict the best protocol that confers a very good immune response against HPV infection. We finally tested the in silico results through in vivo experiments on mice, finding good agreement.

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