Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose.
- Journal Article
Summary
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
Publication
Researcher Affiliations
- Department of Pathology and Microbiology and Immunology, Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
- Tulane National Primate Research Center, Covington, LA 70433, USA.
- Department of Microbiology and Immunology and World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA.
- Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
- Department of Health, Safety and Environment, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
- Tulane National Primate Research Center, Covington, LA 70433, USA.
- Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA 70112, USA.
- 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
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