Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares.
Abstract: In general, vaccines containing inactivated equine herpesvirus-1 (EHV-1) fail to prevent abortion in pregnant mares following infection with a virulent strain of EHV-1. We have tested the hypothesis that resistance to EHV-1-induced abortion in pregnant mares is associated with high frequencies of EHV-1 specific, major histocompatibility complex (MHC) class I-restricted, cytotoxic T lymphocytes (CTL) in the circulation. To test this theory, three groups of pregnant mares were assembled with varying backgrounds of infection or vaccination in an attempt to mimic the immune status of the general population. Group 1 mares (n=9) were untreated controls selected at random. Group 2 mares (n=5) were vaccinated three times intramuscularly with inactivated EHV-1. Group 3 mares (n=3) had been infected with EHV-1 on four previous occasions. The frequency of CTL in blood leucocytes was measured by limiting dilution analysis at three time points; at the beginning of pregnancy (approximately 28 weeks before infection) in the Group 2 and Group 3 mares (4-7 weeks of gestation) (Group 1 was unavailable for sampling) and then 2 weeks before (30-40 weeks of gestation) and 3 weeks after experimental infection in all the mares. Serum samples were collected to monitor complement fixing (CF) antibody titres. Mares in all three groups were infected experimentally with EHV-1 strain Ab4/8 by the intranasal route after which they were monitored clinically to determine the outcome of pregnancy and samples were collected to determine the duration of nasopharyngeal shedding and cell-associated viraemia. The untreated control mares showed low pre-infection CTL. After experimental infection, they all seroconverted, aborted and demonstrated expected clinical and virological signs. Some vaccinated mares (3/5) had elevated titres of CF antibody prior to their first vaccination. All the vaccinated mares seroconverted after vaccination and exhibited higher CTL frequencies than controls before infection. Four of the five foaled normally. The multiply infected mares had low CF antibody titres prior to infection and showed neither seroconversion nor clinical or virological signs after infection. All multiply infected mares exhibited high frequencies of CTL before infection and they all foaled normally. The CTL frequencies observed differed significantly from the expected frequencies in the control and multiply infected groups at 2 weeks pre-infection (P=0.034) and between the foaling and aborting mares at 2 weeks pre-infection (P=0.005) and 3 weeks post-infection (P=0.015). The results show a positive correlation between the number of virus-specific CTL in the peripheral blood of pregnant mares and their protection against abortion induced by EHV-1 infection. Therefore, as indicated by this study, rational approaches to the development of new vaccines for EHV-1 should stimulate cytotoxic immune responses and develop virus-specific CTL as pre-requisites for protection against abortion.
Publication Date: 2003-11-01 PubMed ID: 14592733DOI: 10.1016/j.vetimm.2003.08.004Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates whether the frequency of specific cytotoxic T lymphocytes (CTL) in the bloodstream of pregnant horses links to resistance against abortion triggered by the equine herpesvirus-1 (EHV-1). The study findings support a positive correlation, suggesting that future vaccination strategies for EHV-1 should aim to stimulate such immune responses.
Research Methods
- The researchers assembled three groups of pregnant mares with different levels of past infection or vaccination to reflect the varied immune status in general populations.
- Mares in Group 1 were untreated controls chosen randomly (9 mares); those in Group 2 had been inoculated three times using inactivated EHV-1 (5 mares); while the mares in Group 3 had been infected with EHV-1 on four previous occasions (3 mares).
- The measurement of CTL frequencies in circulating leukocytes was made using limiting dilution analysis at three different time points.
- Blood and serum samples were collected to monitor antibody titres and the frequency of CTL. The groups were then subjected to an experimental EHV-1 infection.
- Post-infection, the pregnancy outcome, duration of nasopharyngeal shedding, and cell-associated viremia were assessed.
Key Findings
- All untreated control mares showed low CTL before infection and, after experimental infection, they all aborted and displayed expected symptoms.
- Some of the vaccinated mares already had elevated antibody levels before the vaccination. Post-vaccination, they all developed new antibodies (seroconversion) and displayed higher CTL frequencies than control mares before infection.
- Mares with multiple past EHV-1 infections had low antibody levels prior to the experiment but showed neither antibody development nor clinical symptoms after infection. They all had a high frequency of CTL before infection and foaled normally.
- Significant differences were observed in CTL frequencies in the control and multiply infected mares before infection and between foaling and aborting mares before and after infection.
Implications and Conclusions
- The research results highlight a positive link between the quantities of virus-specific CTL present in the blood of pregnant mares and their protection against abortion caused by EHV-1 infection.
- This suggests that efficacious strategies for developing new vaccines for EHV-1 should stimulate cytotoxic immune responses and generate virus-specific CTL as prerequisites for offering protection against abortion.
Cite This Article
APA
Kydd JH, Wattrang E, Hannant D.
(2003).
Pre-infection frequencies of equine herpesvirus-1 specific, cytotoxic T lymphocytes correlate with protection against abortion following experimental infection of pregnant mares.
Vet Immunol Immunopathol, 96(3-4), 207-217.
https://doi.org/10.1016/j.vetimm.2003.08.004 Publication
Researcher Affiliations
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. julia.kydd@aht.org.uk
MeSH Terms
- Abortion, Veterinary / immunology
- Abortion, Veterinary / prevention & control
- Abortion, Veterinary / virology
- Animals
- Complement Fixation Tests / veterinary
- Female
- Fever / immunology
- Fever / veterinary
- Fever / virology
- Herpesviridae Infections / blood
- Herpesviridae Infections / immunology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / immunology
- Herpesvirus Vaccines / immunology
- Herpesvirus Vaccines / standards
- Horse Diseases / immunology
- Horse Diseases / virology
- Horses
- Pregnancy
- Statistics, Nonparametric
- T-Lymphocytes, Cytotoxic / immunology
- T-Lymphocytes, Cytotoxic / virology
- Vaccination / veterinary
- Viremia / immunology
- Viremia / veterinary
- Viremia / virology
- Virus Shedding / immunology
Citations
This article has been cited 22 times.- Biondi V, Landi A, Pugliese M, Merola G, Passantino A. Inflammatory Response and Electrocardiographic Examination in Horses Vaccinated against Equine Herpesvirus (Ehv-1). Animals (Basel) 2022 Mar 19;12(6).
- Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1. Front Vet Sci 2021;8:674850.
- Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, Soboll Hussey G. Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses. Viruses 2021 Feb 24;13(3).
- Zarski LM, Weber PSD, Lee Y, Soboll Hussey G. Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection. Pathogens 2021 Jan 7;10(1).
- Stasiak K, Dunowska M, Rola J. Outbreak of equid herpesvirus 1 abortions at the Arabian stud in Poland. BMC Vet Res 2020 Oct 6;16(1):374.
- Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and Disease. J Virol 2019 Nov 15;93(22).
- Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE, Rollins A, Osterrieder N, Goodman LB, Glaser A, Wagner B. The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses. PLoS One 2018;13(11):e0206679.
- Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H, Watts C, Rollins A, Osterrieder N, Wagner B. Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity. BMC Vet Res 2018 Aug 22;14(1):245.
- Liu SA, Stanfield BA, Chouljenko VN, Naidu S, Langohr I, Del Piero F, Ferracone J, Roy AA, Kousoulas KG. Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice. J Virol 2017 Jun 15;91(12).
- 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.
- Huang T, Lehmann MJ, Said A, Ma G, Osterrieder N. Major histocompatibility complex class I downregulation induced by equine herpesvirus type 1 pUL56 is through dynamin-dependent endocytosis. J Virol 2014 Nov;88(21):12802-15.
- Ma G, Feineis S, Osterrieder N, Van de Walle GR. Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I. J Virol 2012 Apr;86(7):3554-63.
- Goodman LB, Wimer C, Dubovi EJ, Gold C, Wagner B. Immunological correlates of vaccination and infection for equine herpesvirus 1. Clin Vaccine Immunol 2012 Feb;19(2):235-41.
- 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.
- Wagner B, Burton A, Ainsworth D. Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals. Vet Res 2010 Jul-Aug;41(4):47.
- Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology 2005 Aug 15;339(1):110-26.
- Wagner B, Schnabel CL, Rollins A. Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4. Vaccines (Basel) 2025 Mar 10;13(3).
- Holmes CM, Wagner B. Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1. Viruses 2024 Sep 25;16(10).
- Giessler KS, Goehring LS, Jacob SI, Davis A, Esser MM, Lee Y, Zarski LM, Weber PSD, Hussey GS. Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses. J Gen Virol 2024 May;105(5).
- Soboll-Hussey G, Dorman DC, Burgess BA, Goehring L, Gross P, Neinast C, Osterrieder K, Pusterla N, Lunn DP. Relationship between equine herpesvirus-1 viremia and abortion or equine herpesvirus myeloencephalopathy in domesticated horses: A systematic review. J Vet Intern Med 2024 May-Jun;38(3):1872-1891.
- Pusterla N, Dorman DC, Burgess BA, Goehring L, Gross M, Osterrieder K, Soboll Hussey G, Lunn DP. Viremia and nasal shedding for the diagnosis of equine herpesvirus-1 infection in domesticated horses. J Vet Intern Med 2024 May-Jun;38(3):1765-1791.
- Osterrieder K, Dorman DC, Burgess BA, Goehring LS, Gross P, Neinast C, Pusterla N, Hussey GS, Lunn DP. Vaccination for the prevention of equine herpesvirus-1 disease in domesticated horses: A systematic review and meta-analysis. J Vet Intern Med 2024 May-Jun;38(3):1858-1871.
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