IRES-based Venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice.
Abstract: Venezuelan equine encephalitis virus (VEEV) is an arbovirus that causes periodic outbreaks that impact equine and human populations in the Americas. One of the VEEV subtypes located in Mexico and Central America (IE) has recently been recognized as an important cause of equine disease and death, and human exposure also appears to be widespread. Here, we describe the use of an Internal Ribosome Entry Site (IRES) from encephalomyocarditis virus to stably attenuate VEEV, creating a vaccine candidate independent of unstable point mutations. Mice infected with this virus produced antibodies and were protected against lethal VEEV challenge. This IRES-based vaccine was unable to establish productive infection in mosquito cell cultures or in intrathoracically injected Aedes taeniorhynchus, demonstrating that it cannot be transmitted from a vaccinee. These attenuation, efficacy and safety results justify further development for humans or equids of this new VEEV vaccine candidate.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication Date: 2013-01-22 PubMed ID: 23351391PubMed Central: PMC3767167DOI: 10.1016/j.virol.2012.11.013Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
Summary
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The research article discusses the successful development of a vaccine candidate for Venezuelan equine encephalitis virus (VEEV), a disease affecting both horses and humans, using a unique genetic element called Internal Ribosome Entry Site (IRES). The vaccinated mice developed immunity against the lethal VEEV infection and the vaccine could not be transmitted from vaccinated individuals, reflecting its potential safety and efficacy for further development.
Objective of the Research
- The major aim of this study is to develop a reliable vaccine candidate to combat Venezuelan equine encephalitis virus (VEEV). The vaccine is based on an innovative approach using the Internal Ribosome Entry Site (IRES) of encephalomyocarditis virus, which help in reducing the harmful effects of VEEV.
Methodology and Findings
- The researchers adopted the Internal Ribosome Entry Site (IRES) from encephalomyocarditis virus to successfully weaken the VEEV.
- The weakened VEEV was then used to create a vaccine that was independent of unstable point mutations, enhancing its reliability and stability.
- The vaccine was then administered to mice which resulted in the production of antibodies, and the mice were protected against fatal VEEV challenge, demonstrating the vaccine’s effectiveness.
- Furthermore, they investigated whether this vaccine could establish a productive infection in mosquito cell cultures, or in intrathoracically injected Aedes taeniorhynchus. The results indicated that it couldn’t, showing that the vaccine cannot be transmitted from the vaccinated host—increasing its safety profile.
Conclusions
- The research concludes by stating the the benefits observed in the experiment—particularly relating to vaccine effectiveness and its lack of transmission capability—demonstrate the potential for the vaccine’s future development for human and equine application.
- This could be a significant step towards preventing periodic outbreaks of VEEV that has harmful impacts on both equine and human populations in the Americas.
Cite This Article
APA
Rossi SL, Guerbois M, Gorchakov R, Plante KS, Forrester NL, Weaver SC.
(2013).
IRES-based Venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice.
Virology, 437(2), 81-88.
https://doi.org/10.1016/j.virol.2012.11.013 Publication
Researcher Affiliations
- Institute of Human Infection and Immunity, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555-0610, USA. slrossi@utmb.edu
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Disease Models, Animal
- Encephalitis Virus, Venezuelan Equine / genetics
- Encephalitis Virus, Venezuelan Equine / immunology
- Encephalomyelitis, Venezuelan Equine / immunology
- Encephalomyelitis, Venezuelan Equine / prevention & control
- Encephalomyocarditis virus / genetics
- Mice
- Protein Biosynthesis
- Survival Analysis
- Vaccination / adverse effects
- Vaccination / methods
- Vaccines, Attenuated / administration & dosage
- Vaccines, Attenuated / adverse effects
- Vaccines, Attenuated / genetics
- Vaccines, Attenuated / immunology
- Vaccines, Synthetic / administration & dosage
- Vaccines, Synthetic / adverse effects
- Vaccines, Synthetic / genetics
- Vaccines, Synthetic / immunology
- Viral Vaccines / administration & dosage
- Viral Vaccines / adverse effects
- Viral Vaccines / genetics
- Viral Vaccines / immunology
Grant Funding
- U54 AI057156 / NIAID NIH HHS
- AI007536-12 / NIAID NIH HHS
- T32 AI007536 / NIAID NIH HHS
- AI007536-11 / NIAID NIH HHS
- T32 AI007526 / NIAID NIH HHS
- T32AI7526-11 / NIAID NIH HHS
- U54AIO57156 / PHS HHS
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