Envelope protein E1 as vaccine target for western equine encephalitis virus.
Abstract: Western equine encephalitis virus (WEEV) is a mosquito-borne RNA virus which causes lethal infection in humans and equines. There are no commercial vaccines or anti-WEEV drugs available for humans. We used replication-defective, human adenovirus serotype-5 (HAd5) as a delivery vector for developing WEEV vaccine. Our previous study found delivery of both E1 and E2 envelope proteins of WEEV by HAd5 vector offers complete protection against lethal challenge of WEEV. In this paper, we constructed a HAd5-vectored E1 vaccine, Ad5-E1. Mice given single-dose vaccination of Ad5-E1 were completely protected against both homologous and heterologous WEEV strains. The protection was rapid, which was achieved as early as day 7 after vaccination. In addition, Ad5-E1 induced a strong WEEV-specific T cell response. Our data suggest E1 is a potential target for developing single-dose, fast-acting, HAd5-vectored vaccine for WEEV.
Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.
Publication Date: 2010-12-03 PubMed ID: 21084062DOI: 10.1016/j.vaccine.2010.11.009Google Scholar: Lookup
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- Journal Article
Summary
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This research investigates the use of envelope protein E1 as a potential target for a rapid-acting, single-dose vaccine for the Western equine encephalitis virus (WEEV), a life-threatening mosquito-borne virus that currently lacks commercial vaccines or drugs for human use.
Objective of the Study
- The study aimed to construct an effective vaccine for the Western equine encephalitis virus (WEEV) which is a severe mosquito-borne RNA virus that afflicts humans and equines but has no existing human-specific commercial vaccines or drugs.
Methodology
- Researchers used defective adenoviruses, specifically human adenovirus serotype-5 (HAd5), as a delivery vector for the WEEV vaccine. The chosen adenovirus is regarded as safe as it can’t reproduce and cause illness in humans.
- Building on their previous research, the team created a HAd5-vectored E1 vaccine known as Ad5-E1, which delivers key WEEV envelope protein E1.
- They had earlier recognized that the dual delivery of WEEV proteins E1 and E2 using a HAd5 vector could provide complete virus protection, leading them to further examine the effectiveness of a single-protein (E1) approach.
Findings
- The research showed that even a single-dose vaccination of Ad5-E1 could fully protect mice against various (homologous and heterologous) strains of WEEV.
- Notably, this protection was not just complete but also rapid, being observed as early as 7 days post-vaccination.
- Besides affording protection, Ad5-E1 was able to stimulate a strong WEEV-specific T cell response, important for boosting the body’s immune system against the virus.
Interpretation and Implication
- The research results suggest that envelope protein E1 presents a potential target for WEEV vaccine development, with Ad5-E1 offering a promising approach for the creation of a fast-acting, single-dose vaccine.
- This has critical implications for mitigating the spread and impact of WEEV, especially given the absence of commercial vaccines or therapeutics for humans.
Cite This Article
APA
Swayze RD, Bhogal HS, Barabé ND, McLaws LJ, Wu JQ.
(2010).
Envelope protein E1 as vaccine target for western equine encephalitis virus.
Vaccine, 29(4), 813-820.
https://doi.org/10.1016/j.vaccine.2010.11.009 Publication
Researcher Affiliations
- Defence Research and Development Canada - Suffield, Box 4000, Station Main, Medicine Hat, Alberta T1A 8K6, Canada.
MeSH Terms
- Adenoviruses, Human / genetics
- Animals
- Antibodies, Neutralizing / blood
- Antibodies, Viral / blood
- Disease Models, Animal
- Drug Carriers
- Encephalitis Virus, Western Equine / immunology
- Encephalomyelitis, Equine / immunology
- Encephalomyelitis, Equine / prevention & control
- Female
- Genetic Vectors
- Humans
- Mice
- Mice, Inbred BALB C
- Neutralization Tests
- Survival Analysis
- T-Lymphocytes / immunology
- Viral Envelope Proteins / immunology
- Viral Plaque Assay
- Viral Vaccines / immunology
Citations
This article has been cited 6 times.- Sutton MS, Pletnev S, Callahan V, Ko S, Tsybovsky Y, Bylund T, Casner RG, Cerutti G, Gardner CL, Guirguis V, Verardi R, Zhang B, Ambrozak D, Beddall M, Lei H, Yang ES, Liu T, Henry AR, Rawi R, Schön A, Schramm CA, Shen CH, Shi W, Stephens T, Yang Y, Florez MB, Ledgerwood JE, Burke CW, Shapiro L, Fox JM, Kwong PD, Roederer M. Vaccine elicitation and structural basis for antibody protection against alphaviruses.. Cell 2023 Jun 8;186(12):2672-2689.e25.
- Torres-Ruesta A, Chee RS, Ng LFP. Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape.. Microorganisms 2021 Apr 22;9(5).
- Stromberg ZR, Fischer W, Bradfute SB, Kubicek-Sutherland JZ, Hraber P. Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses.. Vaccines (Basel) 2020 Jun 3;8(2).
- Rico AB, Phillips AT, Schountz T, Jarvis DL, Tjalkens RB, Powers AM, Olson KE. Venezuelan and western equine encephalitis virus E1 liposome antigen nucleic acid complexes protect mice from lethal challenge with multiple alphaviruses.. Virology 2016 Dec;499:30-39.
- Hülseweh B, Rülker T, Pelat T, Langermann C, Frenzel A, Schirrmann T, Dübel S, Thullier P, Hust M. Human-like antibodies neutralizing Western equine encephalitis virus.. MAbs 2014 May-Jun;6(3):718-27.
- Toth AM, Geisler C, Aumiller JJ, Jarvis DL. Factors affecting recombinant Western equine encephalitis virus glycoprotein production in the baculovirus system.. Protein Expr Purif 2011 Dec;80(2):274-82.
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