Dissertation
A STUDY ON THE POTENTIAL OF MULTIVALENT VIRUS PARTICLE VACCINES
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000005502
Handle:
https://hdl.handle.net/2376/118964
Abstract
A STUDY ON THE POTENTIAL OF MULTIVALENT PSEUDOTYPED VESICULAR STOMATITIS VIRUS AND VIRUS-LIKE PARTICLE VACCINES
By Ithinji Duncan GitongaWashington State University
August 2020
Chair: Kawula, Thomas Hardin
Mostly, studies and vaccines produced for Nipah virus (NiV), Hendra virus (HeV), Ebola virus (EBOV), Rift valley fever virus (RVFV), Peste des petits ruminants virus (PPRV) and Goat pox virus (GTPV) focus on an individual virus, although there is frequently a geographical overlap of these viruses and their hosts. Indeed, the Pteropus bats that harbor NiV and HeV have a wide distribution in Australia, Asia, South America and Africa while RVFV, PPRV and GTPV have an overlapping distribution in Africa and Middle East. These scenarios make combined vaccines feasible. In this study, we incorporated immunogenic proteins from different viruses onto virus-like particles (VLPs) or a replication-incompetent pseudotyped Vesicular Stomatitis virus (VSV) for use as candidate multivalent vaccines. For a start, we optimized incorporation of NiV F, G, HeV F, G and EBOV Gp surface glycoproteins onto VLPs or the pseudotyped VSV. Secondly, we optimized incorporation of RVFV GnGc, PPRV F, H and GTPV P32 surface glycoproteins onto VLPs or the replication-incompetent pseudotyped VSV. Also, we enhanced the candidate vaccines’ thermotolerance via lyophilization with carbohydrates to improve their applicability in environments which lack a cold chain infrastructure. The NiV-HeV-EBOV vaccine elicited neutralizing antibodies against all three viruses in hamsters and protected them against challenge with either NiV, HeV or EBOV. The RVFV-PPRV-GTPV vaccine elicited neutralizing antibodies against the three viruses in mice and is getting tested in goats. Determination of protection against RVFV challenge in mice and immune responses to the three viruses in goats is underway. The NiV-HeV-EBOV vaccine is targeted for use in humans and RVFV-PPRV-GTPV vaccine for use in animals.
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Details
- Title
- A STUDY ON THE POTENTIAL OF MULTIVALENT VIRUS PARTICLE VACCINES
- Creators
- Duncan Gitonga Ithinji
- Contributors
- Kawula T Hardin (Advisor)Hector Aguilar-Carreno (Advisor)Njenga M Kariuki (Committee Member)Mealey Bob (Committee Member)Nicola Anthony (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 90
- Identifiers
- 99900592259201842
- Language
- English
- Resource Type
- Dissertation