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Open AccessArticle

Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose

1
Department of Pathology and Microbiology and Immunology, Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
2
Tulane National Primate Research Center, Covington, LA 70433, USA
3
Department of Microbiology and Immunology and World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA
4
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
5
Department of Health, Safety and Environment, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
6
Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA 70112, USA
7
World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA
8
Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA
9
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Authors to whom correspondence should be addressed.
Vaccines 2020, 8(3), 497; https://doi.org/10.3390/vaccines8030497
Received: 19 July 2020 / Revised: 31 August 2020 / Accepted: 31 August 2020 / Published: 2 September 2020
(This article belongs to the Section Vaccines against Infectious Diseases)
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. View Full-Text
Keywords: Venezuelan equine encephalitis virus; vaccine; internal ribosome entry site; primates Venezuelan equine encephalitis virus; vaccine; internal ribosome entry site; primates
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MDPI and ACS Style

Rossi, S.L.; Russell-Lodrigue, K.E.; Plante, K.S.; Bergren, N.A.; Gorchakov, R.; Roy, C.J.; Weaver, S.C. Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose. Vaccines 2020, 8, 497. https://doi.org/10.3390/vaccines8030497

AMA Style

Rossi SL, Russell-Lodrigue KE, Plante KS, Bergren NA, Gorchakov R, Roy CJ, Weaver SC. Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose. Vaccines. 2020; 8(3):497. https://doi.org/10.3390/vaccines8030497

Chicago/Turabian Style

Rossi, Shannan L.; Russell-Lodrigue, Kasi E.; Plante, Kenneth S.; Bergren, Nicholas A.; Gorchakov, Rodion; Roy, Chad J.; Weaver, Scott C. 2020. "Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose" Vaccines 8, no. 3: 497. https://doi.org/10.3390/vaccines8030497

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