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Veterinary immunology and immunopathology1997; 57(3-4); 201-214; doi: 10.1016/s0165-2427(96)05749-2

Cell-mediated cytolysis of equine herpesvirus-infected cells by leukocytes from young vaccinated horses.

Abstract: The objective of this study was to determine whether the administration of modified-live equine herpesvirus (EHV-1) to young horses with residual maternal antibodies stimulated EHV-specific cytolytic responses, and whether these responses were crossreactive between EHV-1 and EHV-4. Eighteen clinically normal Belgian cross-foals were used in the study and were commingled in two adjacent pens. Skin biopsies were harvested from 16 foals within 24 h of birth and fibroblast cultures were established, expanded and cryopreserved. Beginning at approximately 10 weeks of age, 10 randomly chosen foals were inoculated on days 0, 21, and 43 of the study with a vaccine containing modified-live EHV-1. Blood mononuclear leukocytes were obtained on days 0, 32, and 50 for the assessment of EHV-specific cytolytic activity using 5 h and 18 h chromium release assays. EHV-1-specific antibodies were assessed by enzyme-linked immunosorbent assay using serum collected on days -21, 0, 32, and 50 of the study. Lymphocyte blastogenic tests and bioassays for interferon activity were conducted on day 50. After two vaccinations, mononuclear leukocytes from seven of ten vaccinated foals had cytolytic activity against autologous EHV-1 cells and leukocytes from six of ten lysed EHV-4-infected cells when tested in an 18 h assay. This activity was enhanced by exogenous interleukin 2 and was markedly reduced using target cells from unrelated horses. Cytotoxicity was not detected in a 5 h assay following in vitro stimulation of leukocytes. After three vaccinations, blood leukocytes from 6/6 vaccinated foals and 0/6 unvaccinated foals had proliferative responses EHV-1. There were no significant differences in interferon production by leukocytes from these foals. Twelve foals tested had low concentrations of (maternal) EHV-1-specific antibody prior to vaccination. Five of eight foals tested had increases in EHV-specific antibodies, while 4/4 commingled unvaccinated foals had a decrease or no change in EHV-specific antibodies. These results demonstrate cytotoxic cellular immune responses can be induced in young horses with maternal antibodies following administration of modified-live vaccine.
Publication Date: 1997-07-01 PubMed ID: 9261959DOI: 10.1016/s0165-2427(96)05749-2Google Scholar: Lookup
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  • Journal Article

Summary

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The study investigated whether young horses, still carrying residual maternal antibodies, could produce an immune response to a modified version of equine herpesvirus (EHV-1) through vaccination, and if so, if this response was cross-reactive with another variant, EHV-4. The results suggested that certain immune cells in vaccinated young horses developed the ability to destroy cells infected with both the EHV-1 and EHV-4 viruses.

Methodology

  • The study was conducted on 18 healthy young Belgian cross-foals, who were grouped into two adjacent pens. Skin cells were collected from 16 foals within 24 hours of birth to establish fibroblast cultures, which were later frozen and stored.
  • At around 10 weeks old, 10 foals chosen at random were vaccinated on the 0th, 21st, and 43rd day of the study, with a vaccine containing a modified version of EHV-1.
  • On days 0, 32, and 50 of the study, blood cells known as leukocytes (part of the immune response) were collected. They were then put through chromium release assays – laboratory tests designed to measure how effectively these cells destroyed virus-infected cells.
  • Serum was also collected on certain days to determine the presence of EHV-1-specific antibodies via an enzyme-linked immunosorbent assay (another form of laboratory test).
  • Further tests on day 50 included lymphocyte blastogenic tests and bioassays for interferon activity, both of which are used to characterize the immune response.

Results

  • After two rounds of vaccination, leukocytes from most of the vaccinated foals (7 of out 10) displayed cytolytic activity against cells infected with EHV-1. A smaller number (6 out of 10) were observed to destroy cells infected with EHV-4. This viral destruction capability was enhanced with the addition of a signaling molecule known as interleukin 2 (IL-2).
  • Interestingly, this cytotoxic action was significantly reduced when the target of the leukocytes was cells from unrelated horses, indicating a certain degree of immunity was developed.
  • After three rounds of vaccination, a clear divide was seen between the vaccinated and unvaccinated foals, with all 6 vaccinated foals demonstrating a proliferative response to EHV-1, while none of the unvaccinated foals did so. A similar immune response was seen in the rate of interferon production.
  • At the beginning of the study, 12 foals were found to have low concentrations of pre-existing (maternal) EHV-1-specific antibodies. Post-vaccination, an increase in EHV-specific antibodies was observed in about half the tested foals, while the unvaccinated foals either showed a decrease or no change in these specific antibodies.

Conclusions

  • The study concluded that a cellular immune response can indeed be triggered in young horses still carrying maternal antibodies following the administration of a modified-live vaccine. This was evidenced by the increased cytolytic activities observed in vaccinated foals when exposed to EHV-infected cells.
  • Furthermore, this response was not limited to just EHV-1 but also extended to EHV-4, indicating a cross-reactive potential with different types of the equine herpesvirus.

Cite This Article

APA
Ellis JA, Steeves E, Wright AK, Bogdan JR, Davis WC, Kanara EW, Haines DM. (1997). Cell-mediated cytolysis of equine herpesvirus-infected cells by leukocytes from young vaccinated horses. Vet Immunol Immunopathol, 57(3-4), 201-214. https://doi.org/10.1016/s0165-2427(96)05749-2

Publication

ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 57
Issue: 3-4
Pages: 201-214

Researcher Affiliations

Ellis, J A
  • Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Canada.
Steeves, E
    Wright, A K
      Bogdan, J R
        Davis, W C
          Kanara, E W
            Haines, D M

              MeSH Terms

              • Animals
              • Antibodies, Viral / biosynthesis
              • Antibodies, Viral / immunology
              • Cells, Cultured
              • Cytotoxicity, Immunologic
              • Fibroblasts / immunology
              • Fibroblasts / virology
              • Herpesviridae Infections / immunology
              • Herpesviridae Infections / veterinary
              • Herpesvirus 1, Equid / immunology
              • Horse Diseases / immunology
              • Horses
              • Immunity, Cellular
              • Immunophenotyping / veterinary
              • Interferons / biosynthesis
              • Leukocytes, Mononuclear / immunology
              • Leukocytes, Mononuclear / virology
              • Lymphocyte Activation
              • Random Allocation
              • Viral Vaccines / immunology

              Citations

              This article has been cited 3 times.
              1. Nielsen SS, Alvarez J, Bicout DJ, Calistri P, Canali E, Drewe JA, Garin-Bastuji B, Gonzales Rojas JL, Gortázar C, Herskin M, Michel V, Miranda Chueca MÁ, Roberts HC, Padalino B, Pasquali P, Spoolder H, Ståhl K, Calvo AV, Viltrop A, Winckler C, Carvelli A, Paillot R, Broglia A, Kohnle L, Baldinelli F, Van der Stede Y. Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): infection with Equine Herpesvirus-1. EFSA J 2022 Jan;20(1):e07036.
                doi: 10.2903/j.efsa.2022.7036pubmed: 35035581google scholar: lookup
              2. Kim SK, Shakya AK, O'Callaghan DJ. Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge. J Virol 2016 Sep 15;90(18):8090-104.
                doi: 10.1128/JVI.00986-16pubmed: 27356904google scholar: lookup
              3. Smith PM, Zhang Y, Jennings SR, O'Callaghan DJ. Characterization of the cytolytic T-lymphocyte response to a candidate vaccine strain of equine herpesvirus 1 in CBA mice. J Virol 1998 Jul;72(7):5366-72.