Conclusions: All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared... Show moreConclusions: All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared to the plaque reduction neutralization test, the sensitivity of the Immune Fluorescence Assay test was low. Further research is needed to ascertain that 17D vaccination in immune-compromised patients is safe. (C) 2016 Elsevier Ltd. All rights reserved. Show less
The topics in this thesis revolve around a group of plus-strand RNA viruses that belong to the Flavivirus genus, a general introduction of which is presented in Chapter 1. The experimental chapters... Show moreThe topics in this thesis revolve around a group of plus-strand RNA viruses that belong to the Flavivirus genus, a general introduction of which is presented in Chapter 1. The experimental chapters in this thesis mainly focus on the construction and characterization of flavivirus infectious clones and the application of these useful tools to address fundamental questions on virus biology or to explore novel vaccine platforms based on the yellow fever virus vaccine strain (YFV-17D). Chapter 2 describes the construction and characterization of recombinant YFV-17D viruses expressing Lassa virus (LASV) glycoprotein coding sequences as bivalent vaccine candidates against wildtype YFV and LASV that circulate in the same region in West Africa. Chapter 3 describes the construction and characterization of an alternative YFV-17D vaccine candidate based on a DNA launched YFV-17D infectious clone, and the study of its immunological characteristics. Chapter 4 describes the construction and characterization of the first NKV (no known vector) flavivirus infectious clone, which was further utilized to study the functional significance of RNA elements present in Modoc virus (MODV) 3__-UTR (untranslated region), as a representative of the NKV flaviviruses. A recently discovered common feature for all flaviviruses is the production of a small flavivirus RNA (sfRNA) in infected cells or animals that results from the incomplete degradation of the viral genome by the host exoribonuclease, XRN-1. XRN-1 was predicted to be stalled by a non-H-type RNA pseudoknot structure that is present is the 3__-UTR of every flavivirus studied thus far. Chapter 5 presents a detailed mutagenesis study of many of the unique sequence and structural characteristics of the XRN-1 stalling site in mosquito-borne flaviviruses using YFV-17D as a model. Chapter 6 describes the establishment of mammalian cell lines that constitutively expressed sfRNA from YFV-17D and WNV. This cell line approach could be valuable to further our understanding of sfRNA function within flavivirus life cycle. Chapter 7 of this thesis is a short epilogue, in which the findings presented in the experimental chapters are summarized and discussed in the context of recently published findings and future research directions are suggested to improve the YFV-17D based vaccine platforms or to address the yet-to-be-solved questions about sfRNA production and function. Show less
In an epoch where every generation travels more frequently and at longer distances than the previous generation, with a mean increase of 30 million travellers per year from 1995 until today,... Show moreIn an epoch where every generation travels more frequently and at longer distances than the previous generation, with a mean increase of 30 million travellers per year from 1995 until today, physicians throughout the world are confronted with new diseases. In absolute numbers, this implies that each year, roughly 4 million travellers appeal to specialised health care, either abroad or at home, because of systemic febrile illness, diarrhoea or dermatologic disorders. During the last decades, travel medicine has evolved into a distinct discipline of Infectious Diseases, eventhough transmission of infectious agents into vulnerable populations through travel has been well know for centuries. Improvement of of protection against travel-related diseases can be achieved through knowledge on the following topics; 1. Epidemiology of travel-related diseases, 2. Morbidity and mortality of these illnesses in specific groups of travellers, 3. Adherence to travel health precautions, 4. Responsivity against vaccination, and 5. Availability of preventive measures, such as vaccines. The research described in this thesis addresses these various topics. Show less
