Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose.
Type
ArticleAuthors
Rossi, Shannan LRussell-Lodrigue, Kasi E

Plante, Kenneth S
Bergren, Nicholas A

Gorchakov, Rodion Viktorovich
Roy, Chad J

Weaver, Scott C

KAUST Department
Research SafetyHealth, Safety & Environment Management
Date
2020-09-02Submitted Date
2020-07-19Permanent link to this record
http://hdl.handle.net/10754/665042
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Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus of human, agriculture, and bioweapon threat importance. No FDA-approved treatment is available to combat Venezuelan equine encephalitis in humans, prompting the need to create a vaccine that is safe, efficacious, and cannot be replicated in the mosquito vector. Here we describe the use of a serotype ID VEEV (ZPC-738) vaccine with an internal ribosome entry site (IRES) to alter gene expression patterns. This ZPC/IRES vaccine was genetically engineered in two ways based on the position of the IRES insertion to create a vaccine that is safe and efficacious. After a single dose, both versions of the ZPC/IRES vaccine elicited neutralizing antibody responses in mice and non-human primates after a single dose, with more robust responses produced by version 2. Further, all mice and primates were protected from viremia following VEEV challenge. These vaccines were also safer in neonatal mice than the current investigational new drug vaccine, TC-83. These results show that IRES-based attenuation of alphavirus genomes consistently produce promising vaccine candidates, with VEEV/IRES version 2 showing promise for further development.Citation
Rossi, S. L., Russell-Lodrigue, K. E., Plante, K. S., Bergren, N. A., Gorchakov, R., Roy, C. J., & Weaver, S. C. (2020). Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose. Vaccines, 8(3), 497. doi:10.3390/vaccines8030497Sponsors
We acknowledge Mathilde Guerbois-Galla for her efforts helping with sequencing and cloning of passaged viruses. We also thank the members of the Animal Resource Center for their assistance with animal husbandry and housing.Publisher
MDPI AGJournal
VaccinesPubMed ID
32887313Additional Links
https://www.mdpi.com/2076-393X/8/3/497ae974a485f413a2113503eed53cd6c53
10.3390/vaccines8030497
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