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Veterinary immunology and immunopathology2009; 135(1-2); 108-117; doi: 10.1016/j.vetimm.2009.11.009

Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease.

Abstract: The control of EHV-1 infection by cytotoxic T-cell responses (CTL) via a reduction in cell associated viremia remains an important goal in horses. Unfortunately, current vaccines are inefficient at inducing these responses. We have identified the immediate early (IE) gene of EHV-1 as a potent stimulator of virus-specific CTL responses in ponies expressing a specific MHC class I serological haplotype (A3/B2). This study was designed to determine if vaccination of A3/B2 MHC I positive ponies with the IE gene could induce protection and immune responses associated with cell mediated immunity. Ponies expressing the MHC-I A3/B2 haplotype (A3/B2 vaccinates) and ponies with a different MHC I haplotype (either non-A3 vaccinates or A3-non-B2 vaccinates) were vaccinated with a recombinant modified vaccinia Ankara (rMVA) vector expressing the IE gene on 3 occasions and vaccinates and unvaccinated controls were challenge infected 8 weeks after the last vaccination. Interferon gamma (IFN-gamma) mRNA and antibody titers were determined throughout the study and clinical signs, nasal virus shedding and viremia were determined following challenge infection. Vaccination of A3/B2 vaccinates conferred significant clinical protection and a significant reduction in EHV-1 viremia. IFN-gamma mRNA increased significantly following vaccination in the A3/B2 vaccinates. Antibody titers remained low until after challenge infection, indicating that no accidental field acquired or recrudescent EHV-1 infection had occurred. In summary, this is an important study showing that vaccination of ponies with the EHV-1 IE protein provides not only reduction in clinical disease but also reduction of cell associated viremia, which is a prerequisite for the prevention of abortion and neurological disease.
Publication Date: 2009-11-24 PubMed ID: 20018383DOI: 10.1016/j.vetimm.2009.11.009Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research discusses a study where ponies were immunized with a vaccine containing the IE gene of EHV-1, a type of virus known to affect horses, which resulted in significant clinical protection from infection and a decrease in cell-associated viremia, a key requirement for preventing severe conditions like abortion and neurological disease.

Objectives and Importance of the Study

  • The primary aim of this study was to control the EHV-1 (Equine herpesvirus type 1) infection in horses through effective vaccines that could stimulate virus-specific cytotoxic T-cell responses. These specialized immune system cells are crucial as they help reduce cell-associated viremia, a condition where viruses enter the bloodstream and spread throughout the body.
  • However, current vaccines have not been efficient in invoking these essential responses. Therefore, the researchers turned toward the IE (Immediate Early) gene of EHV-1 that they identified as a potent stimulant of such responses in certain ponies.
  • The study’s significant relevance lies in its potential to curtail EHV-1 infections which can lead to severe conditions in horses, like abortion and neurological diseases.

Execution of the Study

  • The researchers selected ponies having a specific MHC (Major Histocompatibility Complex) class I serological haplotype A3/B2 for the study. They hypothesized the vaccination with the IE gene could shield these ponies and induce immune responses instrumental in cell-mediated immunity.
  • The ponies were vaccinated with a recombinant modified vaccinia Ankara (rMVA) vector that expressed the IE gene. This was done in three phases, and they were subsequently exposed to an infection eight weeks post the final vaccination.
  • The scientists analyzed IFN-gamma mRNA, which is crucial in immune response, and antibody titers over the duration of the study while monitoring the clinical signs, nasal virus shedding, and viremia post-infection.

Findings and Conclusion

  • The study found that vaccination led to significant clinical protection in vaccinated ponies along with a marked decrease in EHV-1 viremia.
  • In addition, they also witnessed a rise in IFN-gamma mRNA post-vaccination in the ponies. Antibody titers remained relatively low until after infection, which indicated no incidental field acquired or re-emerging EHV-1 infections occurred.
  • These findings indicate that vaccination using the EHV-1 IE gene could be an effective strategy for inducing cytotoxic T-cell responses, thereby significantly reducing clinical disease and cell-associated viremia in horses.

Cite This Article

APA
Soboll G, Breathnach CC, Kydd JH, Hussey SB, Mealey RM, Lunn DP. (2009). Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease. Vet Immunol Immunopathol, 135(1-2), 108-117. https://doi.org/10.1016/j.vetimm.2009.11.009

Publication

ISSN: 1873-2534
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 135
Issue: 1-2
Pages: 108-117
PII: S0165-2427(09)00398-5

Researcher Affiliations

Soboll, G
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Rd, Fort Collins, CO 80523, USA.
Breathnach, C C
  • Department of Veterinary Sciences, University of Kentucky, Lexington, KY 40546, USA.
Kydd, J H
  • School of Veterinary Medicine and Science, University of Nottingham, Loughborough, Leicestershire LE12 5RD, UK.
Hussey, S B
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Rd, Fort Collins, CO 80523, USA.
Mealey, R M
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Lunn, D P
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Rd, Fort Collins, CO 80523, USA. Electronic address: lunnp@mail.colostate.edu.

MeSH Terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Female
  • Genes, Immediate-Early / genetics
  • Genes, Immediate-Early / immunology
  • Genotype
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / prevention & control
  • Herpesviridae Infections / veterinary
  • Herpesvirus 1, Equid / genetics
  • Herpesvirus 1, Equid / immunology
  • Herpesvirus Vaccines / genetics
  • Herpesvirus Vaccines / immunology
  • Herpesvirus Vaccines / therapeutic use
  • Horse Diseases / immunology
  • Horse Diseases / prevention & control
  • Horses / immunology
  • Horses / virology
  • Interferon-gamma / blood
  • Male
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use
  • Vaccinia
  • Viremia / immunology
  • Viremia / veterinary

Citations

This article has been cited 6 times.
  1. Pursell T, Spencer Clinton JL, Tan J, Peng R, Ling PD. Modified vaccinia Ankara expressing EEHV1A glycoprotein B elicits humoral and cell-mediated immune responses in mice.. PLoS One 2022;17(3):e0265424.
    doi: 10.1371/journal.pone.0265424pubmed: 35312707google scholar: lookup
  2. Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry.. Front Microbiol 2019;10:2668.
    doi: 10.3389/fmicb.2019.02668pubmed: 31849857google scholar: lookup
  3. de Vries RD, Rimmelzwaan GF. Viral vector-based influenza vaccines.. Hum Vaccin Immunother 2016 Nov;12(11):2881-2901.
    doi: 10.1080/21645515.2016.1210729pubmed: 27455345google scholar: lookup
  4. Bergmann T, Moore C, Sidney J, Miller D, Tallmadge R, Harman RM, Oseroff C, Wriston A, Shabanowitz J, Hunt DF, Osterrieder N, Peters B, Antczak DF, Sette A. The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires.. Immunogenetics 2015 Nov;67(11-12):675-89.
    doi: 10.1007/s00251-015-0872-zpubmed: 26399241google scholar: lookup
  5. Hussey GS, Goehring LS, Lunn DP, Hussey SB, Huang T, Osterrieder N, Powell C, Hand J, Holz C, Slater J. Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions.. Vet Res 2013 Dec 5;44(1):118.
    doi: 10.1186/1297-9716-44-118pubmed: 24308772google scholar: lookup
  6. Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
    doi: 10.1186/1297-9716-42-23pubmed: 21314906google scholar: lookup