Localization of a protective epitope on a Venezuelan equine encephalomyelitis (VEE) virus peptide that protects mice from both epizootic and enzootic VEE virus challenge and is immunogenic in horses.
Abstract: In order to define more precisely the protective epitope encoded within the first 25 amino acids (aa) of the E2 glycoprotein of the Trinidad donkey strain of Venezuelan equine encephalomyelitis (VEE) virus, we examined the immunogenicity of smaller peptides within the first 19 aa. pep1-9 and pep3-10 elicited virus-reactive antibody, but failed to protect mice from virus challenge. Additionally, pep3-10 was identified by a competitive binding assay using overlapping peptide octamers as the putative binding site of the antipeptide monoclonal antibody (mAb) 1A2B-10. Since the E2 amino-terminal sequence for all VEE subtype viruses is conserved, we tested the protective capacity in mice of passively transferred mAb 1A2B-10 and found it to protect from both epizootic and enzootic VEE virus challenge. Since horses are an important natural host for VEE virus, pep1-19 was used to immunize horses and was found to be immunogenic and to elicit virus-reactive antibody.
Publication Date: 1995-02-01 PubMed ID: 7543231DOI: 10.1016/0264-410x(95)93315-zGoogle Scholar: Lookup
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- Journal Article
Summary
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The research aimed to locate a protective epitope encoded within the first 25 amino acids of the E2 glycoprotein from a specific Venezuelan equine encephalomyelitis (VEE) virus strand, and to test the immunogenicity of smaller peptides within this sequence. The results informed potential VEE virus treatment strategy, demonstrating that certain smaller peptides are immunogenic in horses and can protect mice against both epizootic and enzootic VEE virus.
Objective and Methodology
- The objective of this research was to identify a protective epitope, a part of an antigen molecule to which an antibody attaches itself, within the first 25 amino acids of a specific E2 glycoprotein from the Trinidad donkey strain of Venezuelan equine encephalomyelitis (VEE) virus.
- The study then examined the immunogenicity of smaller peptides (pep1-9 and pep3-10) within these first 19 amino acids.
- A competitive binding assay, using overlapping peptide octamers, was used to identify the binding site of the antipeptide monoclonal antibody 1A2B-10 within pep3-10.
Outcomes
- While both pep1-9 and pep3-10 elicited virus-reactive antibody responses, they failed to protect mice from the virus challenge.
- The researchers found the binding site of the monoclonal antibody (mAb) 1A2B-10 within the pep3-10 peptide.
- Given that the E2 amino-terminal sequence is conserved across all VEE subtype viruses, the researchers tested the protective capacity of passively transferred mAb 1A2B-10, which was found to protect mice from both epizootic and enzootic strains of VEE.
Further Implications and Findings
- The researchers additionally tested the first 19 amino acids (pep1-19) in horses, as horses are a significant host for the VEE virus.
- It was discovered that the pep1-19 was immunogenic, in that it could stimulate an immune response, and managed to elicit virus-reactive antibodies in the test subjects.
- The findings offer promise for a wider, cross-species application of treatment strategies against VEE.
Cite This Article
APA
Hunt AR, Roehrig JT.
(1995).
Localization of a protective epitope on a Venezuelan equine encephalomyelitis (VEE) virus peptide that protects mice from both epizootic and enzootic VEE virus challenge and is immunogenic in horses.
Vaccine, 13(3), 281-288.
https://doi.org/10.1016/0264-410x(95)93315-z Publication
Researcher Affiliations
- Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.
MeSH Terms
- Animals
- Antibodies, Monoclonal / therapeutic use
- Antibodies, Viral / blood
- Antigens, Viral / immunology
- Encephalitis Virus, Venezuelan Equine / immunology
- Encephalomyelitis, Venezuelan Equine / immunology
- Encephalomyelitis, Venezuelan Equine / prevention & control
- Enzyme-Linked Immunosorbent Assay
- Epitopes / analysis
- Epitopes / immunology
- Female
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horses
- Immunization, Passive
- Mice
- Peptide Fragments / immunology
- Peptide Fragments / therapeutic use
- Viral Envelope Proteins / immunology
- Viral Envelope Proteins / pharmacology
- Viral Vaccines / immunology
Citations
This article has been cited 11 times.- Calvert AE, Bennett SL, Hunt AR, Fong RH, Doranz BJ, Roehrig JT, Blair CD. Exposing cryptic epitopes on the Venezuelan equine encephalitis virus E1 glycoprotein prior to treatment with alphavirus cross-reactive monoclonal antibody allows blockage of replication early in infection.. Virology 2022 Jan 2;565:13-21.
- Samsa MM, Dupuy LC, Beard CW, Six CM, Schmaljohn CS, Mason PW, Geall AJ, Ulmer JB, Yu D. Self-Amplifying RNA Vaccines for Venezuelan Equine Encephalitis Virus Induce Robust Protective Immunogenicity in Mice.. Mol Ther 2019 Apr 10;27(4):850-865.
- 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.
- Dupuy LC, Richards MJ, Ellefsen B, Chau L, Luxembourg A, Hannaman D, Livingston BD, Schmaljohn CS. A DNA vaccine for venezuelan equine encephalitis virus delivered by intramuscular electroporation elicits high levels of neutralizing antibodies in multiple animal models and provides protective immunity to mice and nonhuman primates.. Clin Vaccine Immunol 2011 May;18(5):707-16.
- Parker MD, Buckley MJ, Melanson VR, Glass PJ, Norwood D, Hart MK. Antibody to the E3 glycoprotein protects mice against lethal venezuelan equine encephalitis virus infection.. J Virol 2010 Dec;84(24):12683-90.
- Hunt AR, Frederickson S, Maruyama T, Roehrig JT, Blair CD. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.. PLoS Negl Trop Dis 2010 Jul 13;4(7):e739.
- Zacks MA, Paessler S. Encephalitic alphaviruses.. Vet Microbiol 2010 Jan 27;140(3-4):281-6.
- Kirsch MI, Hülseweh B, Nacke C, Rülker T, Schirrmann T, Marschall HJ, Hust M, Dübel S. Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV).. BMC Biotechnol 2008 Sep 2;8:66.
- Kolokoltsov AA, Weaver SC, Davey RA. Efficient functional pseudotyping of oncoretroviral and lentiviral vectors by Venezuelan equine encephalitis virus envelope proteins.. J Virol 2005 Jan;79(2):756-63.
- Casadevall A. Passive antibody administration (immediate immunity) as a specific defense against biological weapons.. Emerg Infect Dis 2002 Aug;8(8):833-41.
- Meissner JD, Huang CY, Pfeffer M, Kinney RM. Sequencing of prototype viruses in the Venezuelan equine encephalitis antigenic complex.. Virus Res 1999 Oct;64(1):43-59.
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