Date of Award

Spring 2020

Degree Type

Masters Thesis

Degree Name

Master of Science (MS)

School

Biological, Environmental, and Earth Sciences

Committee Chair

Dr. Fengwei Bai

Committee Chair School

Biological, Environmental, and Earth Sciences

Committee Member 2

Dr. Shahid Karim

Committee Member 2 School

Biological, Environmental, and Earth Sciences

Committee Member 3

Dr. Alex Flynt

Committee Member 3 School

Biological, Environmental, and Earth Sciences

Abstract

Zika Virus (ZIKV) is a mosquito-transmitted flavivirus that usually causes no symptoms to mild febrile in humans, and it has been regarded as an insignificant pathogen to public health. However, recent outbreaks of ZIKV infection have revealed that ZIKV can cause severe neurological effects in adults, such as Guillain-Barre Syndrome (GBS), and in infants whose mothers acquired the virus during pregnancy, causing Congenital Zika Syndrome (CZS). Currently, no approved vaccine is available and there is a critical need to develop an effective and safe vaccine. While most vaccine developmental strategies target the viral prM-E protein of ZIKV, we aimed to create an attenuated ZIKV by inserting several different nucleotide lengths into the 5’ untranslated region (UTR) of the viral genome. We generated a viable mutated ZIKV virus (Z7) was after inserting a 50-nt sequence into the 5’UTR. We then characterized Z7 by comparing growth kinetics in vivo replication by using qPCR and immunostaining assays in cell cultures. We also measured the infectivity and immunogenicity of Z7 in Ifnar1-/-mice. We found that this mutated virus developed a lower viremia compared to WT ZIKV control but induced a similar level of antibody response. Importantly, one dose of Z7 inoculation can protect the mice from a secondary high dose of ZIKV infection in Ifnar1-/-mice. Together, these results suggest that we have successfully developed an attenuated ZIKV strain, which induces protective immune responses against ZIKV infection in mice.

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