Development of the Live-Attenuated Chikungunya Virus Vaccine Candidate CHIKV-NoLS
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Taylor, Adam
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Mahalingam, Suresh
Zaid, Ali
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Abstract
The causal pathogen of chikungunya virus disease, mosquito-transmitted chikungunya virus (CHIKV), has caused significant global epidemics of arthritic disease over the past two decades. A severe chronic, crippling arthritic condition, CHIKV disease can have a negative impact on a patient's mobility and quality of life. Our earlier research led to the production of CHIKV-NoLS, a live-attenuated CHIKV vaccine candidate that has successfully protected against CHIKV disease in preclinical trials. After receiving one dose, mice immunised with CHIKV-NoLS developed a protective immune response against CHIKV. Additional research has shown the utility of a liposome RNA delivery system for directly delivering the RNA genome of CHIKV-NoLS in vivo and promoting in vivo de novo production of live-attenuated vaccine particles.[...] This thesis provides us with essential information about the development of a new vaccine candidate, CHIKV-NoLS, and illustrates how a clinically relevant booster regimen can overcome the challenges faced by a one dose strategy to provide systemic protection against CHIKV disease. Furthermore, I provide new perspectives on the global progress of CHIKV vaccine development to guide future industrial partnerships and clinical development of the CHIKV-NoLS technology. CHIKV-NoLS may be a promising CHIKV vaccine candidate due to lower reversion risks, reported stability, and longevity of protection against CHIKV infection. CHIKV-NoLS faces a long road ahead because no studies on non-human primates or humans have been conducted. Further research on GM cell lines might be useful to establish universal cell lines for vaccine production.
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Thesis (PhD Doctorate)
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Doctor of Philosophy (PhD)
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School of Pharmacy & Med Sci
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The author owns the copyright in this thesis, unless stated otherwise.
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Subject
Chikungunya virus
vaccine candidate
RNA genome