West Nile Virus Vaccine Development

David Che-Hao Chang (2010). West Nile Virus Vaccine Development PhD Thesis, School of Chemistry and Molecular Biosciences, The University of Queensland.

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Author David Che-Hao Chang
Thesis Title West Nile Virus Vaccine Development
School, Centre or Institute School of Chemistry and Molecular Biosciences
Institution The University of Queensland
Publication date 2010
Thesis type PhD Thesis
Supervisor Alexander Khromykh
Total pages 145
Total colour pages 17
Total black and white pages 128
Subjects 06 Biological Sciences
Abstract/Summary West Nile (WN) virus is a mosquito-transmitted flavivirus that causes a potentially fatal disease in humans, birds and horses. WN virus appeared for the first time in North America (New York) in 1999, and within 5 years this highly pathogenic strain (NY99) of WN had spread across North America. An Australian subtype of WN, Kunjin (KUN), shares 98.5% amino acid homology with the NY99 strain. Despite high homology, KUN is non-fatal and very rarely causes disease in infected humans. Our previous studies have shown that immunisation of mice with a KUN infectious clone plasmid DNA provided solid protection against lethal challenge with WNNY99. In the current study, we generated a novel non-infectious prototype of KUN-based DNA vaccine against WN, pKUNdC/C, which transcribes of two RNA species from separate CMV promoters: (i) capsid-deleted KUN RNA and (ii) mRNA expressing the capsid gene. Cells transfected with pKUNdC/C DNA secretes ‘single-round infectious particles’ (SRIPs) containing packaged capsid-deleted RNA which provides an additional round of infection and replication leading to enhanced expression of immunogenic KUN antigens. Vaccination studies in mice showed that a single gene gun immunization with as little as 20 ng of pKUNdC/C DNA was sufficient to elicit robust humoral and cellular immune response able to completely protect animals against lethal challenge with WNNY99. Gene gun immunization of horses with only 4 μg elicited high titres of neutralising antibodies against both WNNY99 and KUN viruses. The use of the gene gun for the animal immunisation studies proved to be of a significant factor for the delivery of pKUNdC/C DNA into Langerhans cells in the skin tissue, thus efficiently facilitated on the induction of immune responses. These results show that pKUNdC/C is a highly efficient DNA vaccine candidate against WN virus infection, and superior to other non-infectious DNA vaccine candidates. This technology can be readily applied to the development of other flavivirus vaccines, such as Japanese Encephalitis (JE) virus and Dengue.
Keyword west nile virus
kunjin virus
Additional Notes 35, 39, 76, 79-82, 84, 87, 89, 91, 94, 99, 107-108, 116, 128

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Created: Tue, 19 Apr 2011, 00:36:05 EST by Mr David Chang on behalf of Library - Information Access Service