Limited potential for mosquito transmission of genetically engineered, live-attenuated western equine encephalitis virus vaccine candidates.
Abstract: Specific mutations associated with attenuation of Venezuelan equine encephalitis (VEE) virus in rodent models were identified during efforts to develop an improved VEE vaccine. Analogous mutations were produced in full-length cDNA clones of the Cba 87 strain of western equine encephalitis (WEE) virus by site-directed mutagenesis in an attempt to develop an improved WEE vaccine. Isogenic viral strains with these mutations were recovered after transfection of baby hamster kidney cells with infectious RNA. We evaluated two of these strains (WE2102 and WE2130) for their ability to replicate in and be transmitted by Culex tarsalis, the principal natural vector of WEE virus in the United States. Each of the vaccine candidates contained a deletion of the PE2 furin cleavage site and a secondary mutation in the E1 or E2 glycoprotein. Both of these potential candidates replicated in mosquitoes significantly less efficiently than did either wild-type WEE (Cba 87) virus or the parental clone (WE2000). Likewise, after intrathoracic inoculation, mosquitoes transmitted the vaccine candidate strains significantly less efficiently than they transmitted either the wild-type or the parental clone. One-day-old chickens vaccinated with either of the two vaccine candidates did not become viremic when challenged with virulent WEE virus two weeks later. Mutations that result in less efficient replication in or transmission by mosquitoes should enhance vaccine safety and reduce the possibility of accidental introduction of the vaccine strain to unintentional hosts.
Publication Date: 2003-03-19 PubMed ID: 12641414
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- Journal Article
Summary
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This research showcases the development and testing of modified strains of the western equine encephalitis (WEE) virus, which showed reduced replication in mosquitoes and minimal transmission capacity. The purpose is to generate a safer and more effective vaccine against this disease, minimising the risks of accidental transmission to non-targeted hosts.
Overview of the Research Paper
- The aim of this research is to develop a safer and more effective vaccine for the Western Equine Encephalitis (WEE) virus.
- Scientists successfully introduced specific mutations into the WEE virus, using strategies learned from prior operations to attenuate a similar ailment, the Venezuelan equine encephalitis (VEE) virus.
- This was achieved by site-directed mutagenesis, a process by which specific DNA changes can be made, utilising full-length cDNA clones of the Cba 87 strain of WEE virus.
The Developed Strains and Their Evaluation
- The team ulimately derived two strains of WEE virus, WE2102 and WE2130, that possessed the desired mutations.
- These strains were then evaluated for their potential to replicate within, and be transmitted by, Culex tarsalis mosquitoes, the primary carriers of WEE virus in the United States.
- Compared to the wild-type WEE virus and the parent clone, these candidate vaccines showed significantly lower efficiency in replication and transmission.
Assessment of Vaccine Candidates in Chickens
- The candidate vaccines were also tested on one-day-old chickens which, after receiving either WE2102 or WE2130, did not become viremic after being exposed to the virulent WEE virus two weeks later.
- This implies that these vaccine candidates can provide protection against a WEE infection, at least in the case of the younger chickens used in this study.
Implication of the Findings
- The important finding in this study is that the developed vaccine candidate strains exhibit lower efficiency in replication within and transmission by mosquitoes.
- This positive attribute could increase the safety of these prospective vaccines and reduce the likelihood of unintentional transmission to non-target hosts, thereby avoiding potential complications in future vaccination programmes against the WEE virus.
Cite This Article
APA
Turell MJ, O'Guinn ML, Parker MD.
(2003).
Limited potential for mosquito transmission of genetically engineered, live-attenuated western equine encephalitis virus vaccine candidates.
Am J Trop Med Hyg, 68(2), 218-221.
Publication
Researcher Affiliations
- Vector Assessment Branch, Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. michael.turell@det.amedd.army.mil
MeSH Terms
- Animals
- Chickens / virology
- Culex / virology
- Encephalitis Virus, Western Equine / classification
- Encephalitis Virus, Western Equine / genetics
- Encephalitis Virus, Western Equine / immunology
- Encephalitis Virus, Western Equine / pathogenicity
- Encephalomyelitis, Venezuelan Equine / prevention & control
- Encephalomyelitis, Venezuelan Equine / transmission
- Encephalomyelitis, Venezuelan Equine / veterinary
- Female
- Horse Diseases / prevention & control
- Horse Diseases / transmission
- Horses
- Insect Vectors / virology
- Mice
- Mice, Inbred ICR / virology
- Mutagenesis, Site-Directed
- Vaccines, Attenuated / genetics
- Viral Vaccines
Citations
This article has been cited 5 times.- Wang L, Zheng R, Li Z, Zhang L. Western equine encephalitis virus: A comprehensive review of epidemics, transmission, hosts, and strategies for mitigation. Virulence 2025 Dec;16(1):2580162.
- Biselli R, Nisini R, Lista F, Autore A, Lastilla M, De Lorenzo G, Peragallo MS, Stroffolini T, D'Amelio R. A Historical Review of Military Medical Strategies for Fighting Infectious Diseases: From Battlefields to Global Health. Biomedicines 2022 Aug 22;10(8).
- Xing Y, Li X, Gao X, Dong Q. Natural Polymorphisms Are Present in the Furin Cleavage Site of the SARS-CoV-2 Spike Glycoprotein. Front Genet 2020;11:783.
- Guerbois M, Volkova E, Forrester NL, Rossi SL, Frolov I, Weaver SC. IRES-driven expression of the capsid protein of the Venezuelan equine encephalitis virus TC-83 vaccine strain increases its attenuation and safety. PLoS Negl Trop Dis 2013;7(5):e2197.
- Graham RL, Sims AC, Brockway SM, Baric RS, Denison MR. The nsp2 replicase proteins of murine hepatitis virus and severe acute respiratory syndrome coronavirus are dispensable for viral replication. J Virol 2005 Nov;79(21):13399-411.
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