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Vaccines2020; 8(3); 497; doi: 10.3390/vaccines8030497

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

Abstract: 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.
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Publication Date: 2020-09-02 PubMed ID: 32887313PubMed Central: PMC7563393DOI: 10.3390/vaccines8030497Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research focuses on the development of a new vaccine, using an internal ribosome entry site (IRES), to protect against the Venezuelan equine encephalitis virus (VEEV). According to the findings, this vaccine is safe, effective, and it cannot be replicated in the mosquito vector.

Research Overview

The research goal was to develop a vaccine for the Venezuelan equine encephalitis virus (VEEV). This is a re-emerging virus that poses threats to human health and agriculture, and it has also been identified as a potential bioweapon. As currently, there are no FDA-approved treatments available to fight this disease in humans, a vaccine is crucial for prevention.

Vaccine Development

  • The VEEV serotype ID (ZPC-738) vaccine was used in this research. An Internal Ribosome Entry Site (IRES) was used to modify the gene expression patterns. The resulting modified vaccine is referred to as the ZPC/IRES vaccine.
  • The researchers engineered the ZPC/IRES vaccine in two different ways. The differentiating factor between the two methods was the position in which the IRES insertion was placed.
  • The purpose of these genetic modifications was to create a safe and effective vaccine that could not be replicated by mosquito vectors.

Vaccine Efficacy and Safety

  • Both versions of the ZPC/IRES vaccine were administered as a single dose to mice and non-human primates, and both produced neutralizing antibody responses – meaning the immune systems of the test subjects developed defense against the VEEV.
  • Version 2 of the ZPC/IRES vaccine was found to be more effective as it produced more robust immune responses.
  • All vaccinated mice and primates were protected from the disease when exposed to VEEV, signifying the vaccine’s effectiveness.
  • The ZPC/IRES vaccine also exhibited a higher level of safety in neonatal mice compared to the current investigational new drug vaccine, TC-83.

Conclusion

The research concluded that the use of IRES to attenuate alphavirus genomes is promising in the production of vaccines. Given its superior performance in these experiments, VEEV/IRES version 2 is highlighted as a promising candidate for further development and study.

Cite This Article

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

Publication

Vaccines
ISSN: 2076-393X
NlmUniqueID: 101629355
Country: Switzerland
Language: English
Volume: 8
Issue: 3
PII: 497

Researcher Affiliations

Rossi, Shannan L
  • Department of Pathology and Microbiology and Immunology, Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
Russell-Lodrigue, Kasi E
  • Tulane National Primate Research Center, Covington, LA 70433, USA.
Plante, Kenneth S
  • Department of Microbiology and Immunology and World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA.
Bergren, Nicholas A
  • Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Gorchakov, Rodion
  • Department of Health, Safety and Environment, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
Roy, Chad J
  • Tulane National Primate Research Center, Covington, LA 70433, USA.
  • Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA 70112, USA.
Weaver, Scott C
  • World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Grant Funding

  • P51 OD011104 / NIH HHS
  • OD011104 / ORIP NIH HHS
  • AI057156 / NIH HHS

Conflict of Interest Statement

R.G. and S.C.W. hold intellectual property related to the IRES-based attenuation of alphaviruses.

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