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This phase III clinical trial aimed to assess the safety and demonstrate the immunogenicity of a candidate freeze-dried purified Vero cell-based rabies vaccine (PVRV-WIBP) developed for human use. A cohort of 40 participants in stage 1 and 1956 subjects in stage 2 with an age range of 10–50 years were recruited for the phase III clinical trial. For safety analysis in stage 1, 20 participants received either 4-dose or 5-dose regimen of PVRV-WIBP. In stage 2, 1956 subjects were randomly divided into the 5-dose PVRV-WIBP, 5-dose PVRV-LNCD, and 4-dose PVRV-WIBP groups. The serum neutralizing antibody titer against rabies was determined on day 7 or 14 and day 35 or 42. Adverse reactions were recorded for more than 6 months. Most adverse reactions, which were mild and moderate in severity, occurred and resolved within 1 week after each injection in the PVRV-WIBP (4 and 5 doses) and PVRV-LNCD (5 doses) groups. All three groups achieved complete seroconversion 14 days after the initial dose and 14 days after completing the full vaccination schedule, the susceptible subjects in the PVRV-WIBP group (4-dose or 5-dose regimen) displayed higher neutralizing antibody titers against the rabies virus compared to those in the PVRV-LNCD group (5-dose regimen). PVRV-WIBP induced non-inferior immune responses versus PVRV-LNCD as assessed by seroconversion rate. PVRV-WIBP was well tolerated and non-inferior to PVRV-LNCD in healthy individuals aged 10–50 years. The results indicated that PVRV-WIBP (both 4- and 5-dose schedules) could be an alternative to rabies post-exposure prophylaxis.

研究科: 千葉大学大学院融合科学研究科（情報科学専攻）, 学位記番号: 千大院融博甲第工85号

Lanthanide phosphates (LnPO4) are considered as a potential nuclear waste form for immobilization of Pu and minor actinides (Np, Am, and Cm). In that respect, in the recent years we have applied advanced atomistic simulation methods to investigate various properties of these materials on the atomic scale. In particular, we computed several structural, thermochemical, thermodynamic and radiation damage related parameters. From a theoretical point of view, these materials turn out to be excellent systems for testing quantum mechanics-based computational methods for strongly correlated electronic systems. On the other hand, by conducting joint atomistic modeling and experimental research, we have been able to obtain enhanced understanding of the properties of lanthanide phosphates. Here we discuss joint initiatives directed at understanding the thermodynamically driven long-term performance of these materials, including long-term stability of solid solutions with actinides and studies of structural incorporation of f elements into these materials. In particular, we discuss the maximum load of Pu into the lanthanide-phosphate monazites. We also address the importance of our results for applications of lanthanide-phosphates beyond nuclear waste applications, in particular the monazite-xenotime systems in geothermometry. For this we have derived a state-of-the-art model of monazite-xenotime solubilities. Last but not least, we discuss the advantage of usage of atomistic simulations and the modern computational facilities for understanding of behavior of nuclear waste-related materials.

Dissertation, RWTH Aachen University, 2018; Aachen 1 Online-Ressource (xx, 140 Seiten) : Illustrationen (2018). = Dissertation, RWTH Aachen University, 2018, The studies performed in the scope of this dissertation focus on the applications of atomistic simulations for computation of various properties of nuclear waste materials, with the main focus on potential ceramic waste forms such as lanthanide-orthophosphates and zirconiumoxide based pyrochlore-type compounds and some limited studies of nuclear graphite. Here I focus on a set of still poorly understood phenomena with the aim to increase our knowledge on and understanding of the performance of these materials in the context of nuclear waste disposal. The investigated processes include the understanding of radiation damage resistance, elastic, thermodynamics and heat transfer properties of lanthanide-phosphates, especially monazite-type, and pyrochlore-type ceramics. Additionally, special attention was paid to investigation of actinides incorporation into these materials. Some effort has been devoted also to investigation of surface chemistry and radiocarbon migration in nuclear graphite. Using accurate atomistic modeling methods we derived important information that substantially enhance knowledge on ceramic waste forms and nuclear graphite. I extensively investigated radiation damage processes in monazite- and xenotime-type ceramics trying to understand the enhanced radiation damage resistance of these materials. We found similarities in the defects formation and recombination capabilities of monazite and TiO2 rutile with strong indication of density difference between the crystalline solid and the amorphous phases being an important factor behind the enhanced radiation damage resistance of both materials. We also derived an important relationship between the threshold displacement energy and the barrier for defect formation. The simulations of radiation-induced amorphization process allowed for the derivation of the thermodynamical properties of the amorphous phase and the critical amorphization dose of monazite of ∼ 0.2 displacements per atom (dpa). We also systematically computed the heat capacity and the elastic and heat transfer properties of series of lanthanide-phosphates, filling up the existing knowledge gaps. This allowed for understanding the difference between the thermal conductivity of monazite and xenotime as well as tracing the disordering of pyrochlore-type ceramics. Most importantly, I simulated the incorporation of actinides into lanthanide-phosphates and pyrochlore ceramics. This helped to interpret and to understand the relevant experimental data and the mechanism and energetics of the structural incorporation of actinides into these materials. Last, but not least, we also performed investigation of the surface chemistry of nuclear graphite, namely the interaction of simple molecules such as H2O with this material, providing hints for understanding the hydrophilic behavior of nuclear graphite. The simulations of self-diffusion mechanisms of 14C in graphite allowed for the identification of the direct in-plane exchange as the most energetically favorable radiocarbon migration process. All the results demonstrate the importance of atomistic modeling as a fundamental and complementary to the experiment tool for the research on nuclear waste materials., Published by Aachen