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Safety and efficacy of a thymidine kinase negative equine herpesvirus-1 vaccine in young horses.

Abstract: A drug induced equine herpesvirus-1 (EHV-1) mutant lacking thymidine kinase inducing activity was developed and evaluated as a vaccine. The safety and effectiveness of the vaccine to protect against experimentally induced EHV-1 respiratory disease were evaluated in weanling horses free of EHV-1 neutralizing antibody. The vaccine was safe when administered either intramuscularly or intravenously, and EHV-1 was not shed intranasally during the 12 days following administration. Intranasal challenge with virulent EHV-1 was used to evaluate vaccine efficacy. Following challenge, there was a significantly (p less than 0.05) greater increase in peak body temperatures and duration of nasal virus shedding in the nonvaccinates, and a significant (p less than 0.05) increase in serum neutralizing antibody titers in the vaccinates.
Publication Date: 1990-04-01 PubMed ID: 2162730PubMed Central: PMC1255647
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The research article presents the development and evaluation of a new vaccine for equine herpesvirus-1 (EHV-1), engineered using a drug-induced mutant that lacks thymidine kinase activity. The vaccine was tested for safety and effectiveness in young horses that have never been exposed to EHV-1, showing promising results in terms of safety and potential to trigger an immune response.

Creation and Testing of the Vaccine

  • Scientists developed an equine herpesvirus-1 (EHV-1) mutation that doesn’t exhibit thymidine kinase (TK) activity through drug induction. TK is an enzyme that the virus usually uses to replicate, so a TK-negative mutant is expected to have a reduced ability to replicate within a host.
  • The newly developed vaccine was tested on weanling horses, which are young horses that have been weaned from their mothers and have never been exposed to EHV-1. It’s worth noting that this is an ideal target group for such studies, as the young unexposed horses would help determine the vaccine’s effectivity without the influence of prior immunity.

Safety Evaluation

  • The safety of the vaccine was evaluated based on how well the horses tolerated it. The researchers administered the vaccine either via intramuscular injection or intravenous infusion, and both methods proved to be safe.
  • Moreover, there was no detection of EHV-1 being shed through the nasal passage of the horses in the 12 days following vaccination. This indicates that the vaccinated horses did not show signs of infection or active virus replication and shedding, verifying the safety of the vaccine.

Efficacy Evaluation

  • The effectiveness of the vaccine was assessed by exposing the vaccinated horses to virulent EHV-1 and measuring the increase in body temperature and duration of nasal virus shedding (common indicators of infection) in comparison to non-vaccinated horses.
  • The vaccinated horses demonstrated significantly lower increases in body temperature and shorter duration of nasal shedding compared to non-vaccinated horses. Notably, even in the face of this virulent exposure, vaccinated horses’ immune response yielded high titers of EHV-1 neutralizing antibodies. These antibodies are a vital part of the immune response, indicating that the vaccine has successfully triggered the immune system to react against the virus.

Conclusion

The absence of thymidine kinase activity in the new EHV-1 vaccine showed improved safety and efficacy in young horses, reducing signs of infection and inducing an effective immune response. However, more research and broader testing are needed to ensure that this vaccine would be universally effective in horses of all ages and health statuses.

Cite This Article

APA
Cornick J, Martens J, Martens R, Crandell R, McConnell S, Kit S. (1990). Safety and efficacy of a thymidine kinase negative equine herpesvirus-1 vaccine in young horses. Can J Vet Res, 54(2), 260-266.

Publication

ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 54
Issue: 2
Pages: 260-266

Researcher Affiliations

Cornick, J
  • Large Animal Medicine and Surgery, Texas Veterinary Medical Diagnostic Laboratory, Texas A&M University, College Station 77843-4475.
Martens, J
    Martens, R
      Crandell, R
        McConnell, S
          Kit, S

            MeSH Terms

            • Animals
            • Antibodies, Viral / biosynthesis
            • Body Temperature
            • DNA, Viral / analysis
            • Electrophoresis, Agar Gel
            • Enzyme Induction
            • Herpesviridae / immunology
            • Herpesviridae Infections / prevention & control
            • Herpesviridae Infections / veterinary
            • Herpesvirus 1, Equid / enzymology
            • Herpesvirus 1, Equid / genetics
            • Herpesvirus 1, Equid / immunology
            • Horse Diseases / prevention & control
            • Horses
            • Leukocyte Count / veterinary
            • Mutation
            • Neutrophils
            • Restriction Mapping
            • Thymidine Kinase / biosynthesis
            • Thymidine Kinase / genetics
            • Vaccination / veterinary
            • Viral Vaccines / immunology

            Grant Funding

            • K6-AI-2352-24 / NIAID NIH HHS

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            Citations

            This article has been cited 3 times.
            1. Anderson C, Baha H, Boghdeh N, Barrera M, Alem F, Narayanan A. Interactions of Equine Viruses with the Host Kinase Machinery and Implications for One Health and Human Disease.. Viruses 2023 May 13;15(5).
              doi: 10.3390/v15051163pubmed: 37243249google scholar: lookup
            2. Heyn I, Bremer L, Zingler P, Fickenscher H. Self-Repairing Herpesvirus Saimiri Deletion Variants.. Viruses 2022 Jul 13;14(7).
              doi: 10.3390/v14071525pubmed: 35891505google scholar: lookup
            3. Tewari D, Gibson JS, Slater JD, O'Neill T, Hannant D, Allen GP, Field HJ. Modulation of the serological response of specific pathogen-free (EHV-free) foals to EHV-1 by previous infection with EHV-4 or a TK-deletion mutant of EHV-1.. Arch Virol 1993;132(1-2):101-20.
              doi: 10.1007/BF01309846pubmed: 8394686google scholar: lookup