Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine.
Abstract: Equine herpesvirus type 1 (EHV-1) continues to cause severe outbreaks of abortions or myeloencephalopathy in horses despite widely used vaccination. The aim of this work was to determine the effects of frequent vaccination with an inactivated EHV vaccine on immune development in horses. Fifteen EHV-1 naïve mares were vaccinated a total of 5 times over a period of 8 months with intervals of 20, 60, 90 and 60 days between vaccine administrations. Total antibody and antibody isotype responses were evaluated with a new sensitive EHV-1 Multiplex assay to glycoprotein C (gC) and gD for up to 14 months after initial vaccination. Antibodies peaked after the first two vaccine doses and then declined despite a third administration of the vaccine. The fourth vaccine dose was given at 6 months and the gC and gD antibody titers increased again. Mixed responses with increasing gC but decreasing gD antibody values were observed after the fifth vaccination at 8 months. IgG4/7 isotype responses mimicked the total Ig antibody production to vaccination most closely. Vaccination also induced short-lasting IgG1 antibodies to gC, but not to gD. EHV-1-specific cellular immunity induced by vaccination developed slower than antibodies, was dominated by IFN-γ producing T-helper 1 (Th1) cells, and was significantly increased compared to pre-vaccination values after administration of 3 vaccine doses. Decreased IFN-γ production and reduced Th1-cell induction were also observed after the second and fourth vaccination. Overall, repeated EHV vaccine administration did not always result in increasing immunity. The adverse effects on antibody and cellular immunity that were observed here when the EHV vaccine was given in short intervals might in part explain why EHV-1 outbreaks are observed worldwide despite widely used vaccination. The findings warrant further evaluation of immune responses to EHV vaccines to optimize vaccination protocols for different vaccines and horse groups at risk.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication Date: 2015-09-16 PubMed ID: 26384446DOI: 10.1016/j.vaccine.2015.09.009Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research presents an investigation into how frequent vaccination with an inactivated equine herpesvirus (EHV-1) vaccine impacts horses’ immune system responses. Despite the global use of vaccination, EHV-1 continues to cause significant outbreaks of abortions and myeloencephalopathy in horses, suggesting the current approach to immunity development may be insufficient.
Study Design and Protocol
- Utilizing 15 EHV-1 naïve mares, the research team conducted an experimental vaccination program over eight months. The mares were injected with the inactivated EHV-1 vaccine at intervals of 20, 60, 90, and 60 days for a total of five doses.
- Blood samples were taken pre- and post-vaccination for an extended period of up to 14 months from the initial vaccination to measure immune responses.
- The researched focused on evaluating total antibody and antibody isotype responses using a sensitive EHV-1 multiplex assay to glycoprotein C (gC) and gD.
Observations
- Antibodies peaked after the first two injections and then gradually declined despite the continuation of vaccination. A significant surge of antibody titers was noticed after the fourth vaccination at six months.
- A complicated fluctuation was observed post-fifth vaccination with increasing gC but declining gD antibody values.
- The IgG4/7 isotype responses tracked closely with the total Ig antibody production patterns, while the vaccine only led to brief IgG1 antibodies to gC, not to gD.
- The growth of EHV-1-specific cellular immunity prompted by vaccination developed at a slower pace compared to antibodies and was dominated by IFN-γ producing T-helper 1 (Th1) cells. A significant increase compared to pre-vaccination values was found after the third vaccine dose.
- Decreased IFN-γ production and reduced Th1-cell induction were observed after the second and fourth vaccinations.
Conclusions and Implications
- The study concludes that the repeated administration of the EHV vaccine doesn’t always result in gradually increasing immunity. Its adverse effects on both antibody and cellular immunity are noticed when given in shorter intervals, which may partly explain the persistence of EHV-1 outbreaks.
- The authors suggest that these findings are crucial and warrant further evaluation of EHV vaccine-induced immune responses. These results could help to optimize vaccination protocols for various vaccines and at-risk horse groups, which in turn could improve preventive measures against EHV-1.
Cite This Article
APA
Wagner B, Goodman LB, Babasyan S, Freer H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Perkins GA.
(2015).
Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine.
Vaccine, 33(42), 5588-5597.
https://doi.org/10.1016/j.vaccine.2015.09.009 Publication
Researcher Affiliations
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. Electronic address: bw73@cornell.edu.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
- Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavik, Iceland.
- Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavik, Iceland.
- Icelandic Food and Veterinary Authority, MAST, Office of Animal Health and Welfare, 800 Selfoss, Iceland.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Antibody Formation
- CD8-Positive T-Lymphocytes / immunology
- Female
- Herpesviridae Infections / immunology
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid
- Herpesvirus Vaccines / immunology
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horse Diseases / virology
- Horses / immunology
- Immunity, Cellular
- Immunoglobulin G / blood
- Interferon-gamma / immunology
- Neutralization Tests
- Pregnancy
- Th1 Cells / immunology
- Vaccines, Inactivated / immunology
- Viral Envelope Proteins / immunology
Citations
This article has been cited 20 times.- Keller LE, Tait Wojno ED, Begum L, Fortier LA. Interleukin-6 neutralization and regulatory T cells are additive in chondroprotection from IL-1β-induced inflammation. J Orthop Res 2023 May;41(5):942-950.
- Gressler AE, Lübke S, Wagner B, Arnold C, Lohmann KL, Schnabel CL. Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences. Front Immunol 2022;13:896255.
- Schnabel CL, Fletemeyer B, Lübke S, Marti E, Wagner B, Alber G. CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses. Front Immunol 2022;13:805026.
- El Brini Z, Fassi Fihri O, Paillot R, Lotfi C, Amraoui F, El Ouadi H, Dehhaoui M, Colitti B, Alyakine H, Piro M. Seroprevalence of Equine Herpesvirus 1 (EHV-1) and Equine Herpesvirus 4 (EHV-4) in the Northern Moroccan Horse Populations. Animals (Basel) 2021 Sep 29;11(10).
- Cooper CJ, Arroyo LG, Pearl DL, Hewson J, Lillie BN. Survey of the equine broodmare industry, abortion, and equine herpesvirus-1 vaccination in Ontario. Can Vet J 2021 Feb;62(2):124-132.
- Raza F, Ivanek R, Freer H, Reiche D, Rose H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Wagner B. Cul o 2 specific IgG3/5 antibodies predicted Culicoides hypersensitivity in a group imported Icelandic horses. BMC Vet Res 2020 Aug 10;16(1):283.
- Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry. Front Microbiol 2019;10:2668.
- 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.
- Li L, Wagner B, Freer H, Schilling M, Bannantine JP, Campo JJ, Katani R, Grohn YT, Radzio-Basu J, Kapur V. Early detection of Mycobacterium avium subsp. paratuberculosis infection in cattle with multiplex-bead based immunoassays. PLoS One 2017;12(12):e0189783.
- Carossino M, Wagner B, Loynachan AT, Cook RF, Canisso IF, Chelvarajan L, Edwards CL, Nam B, Timoney JF, Timoney PJ, Balasuriya UBR. Equine Arteritis Virus Elicits a Mucosal Antibody Response in the Reproductive Tract of Persistently Infected Stallions. Clin Vaccine Immunol 2017 Oct;24(10).
- Wagner B, Perkins G, Babasyan S, Freer H, Keggan A, Goodman LB, Glaser A, Torsteinsdóttir S, Svansson V, Björnsdóttir S. Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1) at Weanling Age. PLoS One 2017;12(1):e0169072.
- Alpysbayeva SE, Abdykalyk AA, Tileukhanov K, Abdimukhtar AR, Toleukhan AT, Sarmykova MK, Anarbekova AM, Shayakhmetov YA, Syrym NS, Nurabaev SS, Yespembetov BA. Evaluating the Biochemical and Haematological Safety of the Histoplasma capsulatum var. farciminosum '8ZH' Vaccine in Foals. Vet Med Sci 2026 Jan;12(1):e70764.
- 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).
- Wjst VF, Lübke S, Wagner B, Rhyner C, Jentsch MC, Arnold C, Lohmann KL, Schnabel CL. Aspergillus fumigatus antigen-reactive Th17 cells are enriched in bronchoalveolar lavage fluid in severe equine asthma. Front Immunol 2024;15:1367971.
- Schramm A, Ackermann M, Eichwald C, Aguilar C, Fraefel C, Lechmann J. Antibody reactions of horses against various domains of the EHV-1 receptor-binding protein gD1. PLoS One 2024;19(7):e0301987.
- Eady NA, Holmes C, Schnabel C, Babasyan S, Wagner B. Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies. J Virol 2024 Jun 13;98(6):e0025024.
- Kreutzfeldt N, Chambers TM, Reedy S, Spann KM, Pusterla N. Effect of dexamethasone on antibody response of horses to vaccination with a combined equine influenza virus and equine herpesvirus-1 vaccine. J Vet Intern Med 2024 Jan-Feb;38(1):424-430.
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