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Home / Equine Research Bank / Vaccines (Basel) / Multiple Gene Deletion Mutants of Equine Herpesvirus 1 Exhib...
Vaccines2025; 13(1); 45; doi: 10.3390/vaccines13010045

Multiple Gene Deletion Mutants of Equine Herpesvirus 1 Exhibit Strong Protective Efficacy Against Wild Virus Challenge in a Murine Model.

Abstract: Equine herpesvirus type 1 (EHV1) is a ubiquitous viral pathogen infecting the equine population worldwide. EHV1 infection causes respiratory illness, abortion, neonatal foal mortality, and myeloencephalopathy. The currently available modified live EHV1 vaccines have safety and efficacy limitations. The two mutant EHV1 viruses (vToH-DMV (∆IR6/gE) and vToH-QMV (∆IR6/UL43/gE/UL56)), generated by the deletion of genes responsible for virulence (gE and IR6) and immunosuppression (uL43 and uL56), have been previously characterized by our group and found to generate good immune responses. The present study aimed to determine the safety and protective efficacy of the above mutants against a virulent EHV1 challenge in a murine model. Methods: BALB/c mice were intranasally immunized with a live vToH-QMV or vToH-DMV vaccine. Intranasal booster immunization was given at 14 days post-vaccination (dpv). Both mutants induced an optimal level of EHV1-specific humoral and cell-mediated immune responses, as determined by virus neutralization assay, ELISA, and immunophenotyping. At 35 dpv, the mice were intranasally challenged with wild-type EHV1 (vRaj strain). Results: Amongst the two mutants, vToH-QMV induced a better immune response than the vToH-DMV vaccine. Furthermore, vToH-QMV provided good protection in mice against the virulent challenge. It specifically exhibited less severe clinical disease in terms of clinical signs, body weight reduction, and gross and histopathological lung lesions accompanied by early virus clearance. Conclusions: These studies are suggestive of vToH-QMV EHV1 being a potential vaccine candidate against EHV1 infection, which needs to be finally tested in the main host, i.e., horses.
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Publication Date: 2025-01-08 PubMed ID: 39852824PubMed Central: PMC11768829DOI: 10.3390/vaccines13010045Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This research evaluates the safety and protective efficacy of two genetically modified equine herpesvirus 1 (EHV1) mutants as vaccine candidates in mice, with a focus on their ability to induce immune responses and protect against a virulent EHV1 challenge.

Background and Purpose

  • Equine herpesvirus type 1 (EHV1): A common virus affecting horses worldwide, causing serious conditions such as respiratory disease, abortion, newborn foal death, and neurological disorders.
  • Current vaccines: Existing modified live EHV1 vaccines have limitations in terms of safety and effectiveness.
  • Genetically modified mutants: Two mutant viruses were engineered by deleting specific genes:
    • vToH-DMV: Deletion of IR6 and gE genes (genes related to virulence).
    • vToH-QMV: Deletion of IR6, gE, UL43, and UL56 genes (genes related both to virulence and immunosuppression).
  • Previous findings: These mutants were known to stimulate good immune responses in earlier studies.
  • Research goal: To investigate the safety and protective efficacy of vToH-DMV and vToH-QMV in a mouse model exposed to wild-type EHV1.

Methods

  • Animal model: BALB/c mice were used for intranasal immunization with live vaccines (vToH-DMV or vToH-QMV).
  • Vaccination schedule: Initial vaccination followed by an intranasal booster at 14 days post-vaccination (dpv).
  • Immune response evaluation:
    • Virus neutralization assay to detect antibody activity.
    • ELISA (Enzyme-Linked Immunosorbent Assay) to quantify specific antibodies.
    • Immunophenotyping to assess cell-mediated immunity.
  • Challenge experiment: At 35 dpv, vaccinated mice were intranasally infected with a virulent wild-type EHV1 strain (vRaj).

Results

  • Immune responses: Both mutants induced strong humoral (antibody-based) and cell-mediated immune responses, as indicated by laboratory assays.
  • Comparison of mutants: vToH-QMV elicited a stronger immune response than vToH-DMV.
  • Protective efficacy: Mice vaccinated with vToH-QMV showed:
    • Mild clinical symptoms compared to unvaccinated controls.
    • Less body weight loss after the virus challenge.
    • Reduced lung damage, both in gross pathology and microscopic histopathology.
    • Faster clearance of the virus from their systems.

Conclusions and Implications

  • The vToH-QMV triple mutant strain is a promising vaccine candidate demonstrating strong protective immunity against EHV1 in the mouse model.
  • This mutant’s improved safety and efficacy profile may overcome the limitations seen with current live vaccines.
  • Further testing in horses, the natural host, is recommended to confirm its vaccine potential and practical applicability.

Cite This Article

APA
Pradhan SS, Balena V, Bera BC, Anand T, Khetmalis R, Madhwal A, Kandasamy S, Pavulraj S, Bernela M, Mor P, Tripathi BN, Virmani N. (2025). Multiple Gene Deletion Mutants of Equine Herpesvirus 1 Exhibit Strong Protective Efficacy Against Wild Virus Challenge in a Murine Model. Vaccines (Basel), 13(1), 45. https://doi.org/10.3390/vaccines13010045

Publication

Vaccines
ISSN: 2076-393X
NlmUniqueID: 101629355
Country: Switzerland
Language: English
Volume: 13
Issue: 1
PII: 45

Researcher Affiliations

Pradhan, Stephanie S
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
  • Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly 243122, Uttar Pradesh, India.
Balena, Vekataramireddy
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
  • Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly 243122, Uttar Pradesh, India.
Bera, Bidhan Chandra
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
Anand, Taruna
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
Khetmalis, Rhushikesh
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
  • Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly 243122, Uttar Pradesh, India.
Madhwal, Aashwina
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
  • Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly 243122, Uttar Pradesh, India.
Kandasamy, Supriya
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
  • Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly 243122, Uttar Pradesh, India.
Pavulraj, Selvaraj
  • Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
Bernela, Manju
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
Mor, Priya
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.
Tripathi, Bhupendra Nath
  • Indian Council of Agricultural Research, Krishi Bhawan, New Delhi 110012, Delhi, India.
Virmani, Nitin
  • ICAR-National Research Centre on Equines, Sirsa Road, Hisar 125001, Haryana, India.

Grant Funding

  • Nil / Indian Council of Agricultural Research

Conflict of Interest Statement

The authors declare no conflicts of interest.

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Citations

This article has been cited 1 times.
  1. de la Cuesta-Torrado M, Vitale V, Velloso Alvarez A, Neira-Egea P, Diss C, Cuervo-Arango J. The Effect of Vaccination Status on Total Lymphocyte Count in Horses Affected by Equine Herpes Virus-1 Myeloencephalopathy.. Animals (Basel) 2025 Apr 1;15(7).
    doi: 10.3390/ani15071019pubmed: 40218411google scholar: lookup
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