Efficacy of DNA vaccination against western equine encephalitis virus infection.
Abstract: The efficacy of a DNA vaccine against western equine encephalitis (WEE) infection in mice was evaluated. The 26S structural region was expressed, in vitro from an internal T7 promoter using a rabbit reticulysate transcription/translation system; and from a CMV promoter after transfection into Vero cell monolayers. The proteins synthesized were reactive with anti-WEE virus (WEEV) antibodies, both in western blot analysis and histochemical staining, respectively. When the DNA vaccine plasmid, pVHX-6, was administered intraepidermally to mice, followed by challenge in a lethal mouse model, the level of protection obtained ranged from 50 to 100% amongst three strains of WEEV. Preliminary results suggest the protective immunity provided by the DNA vaccine appears to be a cell-mediated immune response, as elevated cytotoxic T lymphocyte activity was detected against the E2 protein in a T-cell proliferation assay. The efficacy results suggest a DNA vaccine may be a promising approach against WEE infection.
Publication Date: 2005-03-10 PubMed ID: 15755611DOI: 10.1016/j.vaccine.2005.01.032Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper is about testing the effectiveness of a DNA vaccine against western equine encephalitis (WEE) virus in mice, showing that it provided a significant level of protection and pointing to the vaccine’s potential for use in preventing WEE infection.
Experiment Procedure
- The researchers created a DNA vaccine using the 26S structural region of the WEE virus. This segment has a critical role in virus replication and hence, forms a significant part of the vaccine.
- This region was expressed in two distinct environments: In vitro from an internal T7 promoter using a rabbit reticulysate transcription/translation system; and from a CMV promoter after transfection into Vero cell monolayers. As a result, the proteins synthesized are expected to interact with WEE virus antibodies.
- The production of the vaccine was checked using western blot analysis and histochemical staining which are common methods for identifying specific proteins in a sample.
Testing the Vaccine on Mice
- The DNA vaccine, labeled as pVHX-6, was administered to mice through the skin (intraepidermally).
- The mice were then exposed to the WEE virus in a lethal mouse model (a model designed to mimic severe infection in humans).
- The level of protection the vaccine provided ranged from 50 to 100% among three different strains of the WEE virus, showing the vaccine could protect against multiple versions of the virus.
Findings on the Protective Immunity
- Preliminary results suggest the vaccine largely works through a cell-mediated immune response. This type of immunity involves immune cells, such as T cells, directly destroying virus-infected cells.
- Increased cytotoxic T lymphocyte activity was observed against the E2 protein – part of the 26S structural region – in a T-cell proliferation assay. This assay measures the number of T cells that are produced when they’re stimulated by an antigen, which in this case, was the E2 protein.
Conclusion
- The research concluded that a DNA vaccine could be a promising method for preventing WEE infection. The vaccine produced a solid immune response and offered substantial protection against the virus in the experimental mice models.
- The DNA vaccine’s cell-mediated immunity and its adaptability to different virus strains make it a potential candidate for further investigation and development.
Cite This Article
APA
Nagata LP, Hu WG, Masri SA, Rayner GA, Schmaltz FL, Das D, Wu J, Long MC, Chan C, Proll D, Jager S, Jebailey L, Suresh MR, Wong JP.
(2005).
Efficacy of DNA vaccination against western equine encephalitis virus infection.
Vaccine, 23(17-18), 2280-2283.
https://doi.org/10.1016/j.vaccine.2005.01.032 Publication
Researcher Affiliations
- Chemical Biological Defence Section, Defence R&D Canada-Suffield, Box 4000, Station Main, Medicine Hat, Alta., Canada T1A 8K6. les.nagata@drdc-rddc.gc.ca
MeSH Terms
- Animals
- Antigens, Viral / genetics
- Chlorocebus aethiops
- Encephalitis Virus, Western Equine / genetics
- Encephalitis Virus, Western Equine / immunology
- Encephalomyelitis, Equine / immunology
- Encephalomyelitis, Equine / prevention & control
- Genetic Vectors
- Lymphocyte Activation
- Mice
- Mice, Inbred BALB C
- Plasmids / genetics
- Rabbits
- T-Lymphocytes, Cytotoxic / immunology
- Vaccines, DNA / genetics
- Vaccines, DNA / pharmacology
- Vero Cells
- Viral Structural Proteins / genetics
- Viral Structural Proteins / immunology
- Viral Vaccines / genetics
- Viral Vaccines / pharmacology
Citations
This article has been cited 12 times.- Phelps AL, O'Brien LM, Ulaeto DO, Holtsberg FW, Liao GC, Douglas R, Aman MJ, Glass PJ, Moyer CL, Ennis J, Zeitlin L, Nagata LP, Hu WG. Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV.. Viruses 2021 Nov 5;13(11).
- 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).
- Dupuy LC, Richards MJ, Livingston BD, Hannaman D, Schmaljohn CS. A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges.. J Immunol Res 2018;2018:8521060.
- 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.
- Teo TH, Lum FM, Lee WW, Ng LF. Mouse models for Chikungunya virus: deciphering immune mechanisms responsible for disease and pathology.. Immunol Res 2012 Sep;53(1-3):136-47.
- Gauci PJ, Wu JQ, Rayner GA, Barabé ND, Nagata LP, Proll DF. Identification of Western equine encephalitis virus structural proteins that confer protection after DNA vaccination.. Clin Vaccine Immunol 2010 Jan;17(1):176-9.
- Atasheva S, Wang E, Adams AP, Plante KS, Ni S, Taylor K, Miller ME, Frolov I, Weaver SC. Chimeric alphavirus vaccine candidates protect mice from intranasal challenge with western equine encephalitis virus.. Vaccine 2009 Jul 9;27(32):4309-19.
- Peng W, Peltier DC, Larsen MJ, Kirchhoff PD, Larsen SD, Neubig RR, Miller DJ. Identification of thieno[3,2-b]pyrrole derivatives as novel small molecule inhibitors of neurotropic alphaviruses.. J Infect Dis 2009 Apr 1;199(7):950-7.
- Wang WW, Das D, Suresh MR. A versatile bifunctional dendritic cell targeting vaccine vector.. Mol Pharm 2009 Jan-Feb;6(1):158-72.
- Kolokoltsova OA, Domina AM, Kolokoltsov AA, Davey RA, Weaver SC, Watowich SJ. Alphavirus production is inhibited in neurofibromin 1-deficient cells through activated RAS signalling.. Virology 2008 Jul 20;377(1):133-42.
- Julander JG, Siddharthan V, Blatt LM, Schafer K, Sidwell RW, Morrey JD. Effect of exogenous interferon and an interferon inducer on western equine encephalitis virus disease in a hamster model.. Virology 2007 Apr 10;360(2):454-60.
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