Intranasal IgG4/7 antibody responses protect horses against equid herpesvirus-1 (EHV-1) infection including nasal virus shedding and cell-associated viremia.
Abstract: Equid herpesvirus-1 (EHV-1) outbreaks continue despite widely used vaccination. We demonstrated previously that an ORF1/ORF71 gene deletion mutant of the EHV-1 strain Ab4 (Ab4ΔORF1/71) is less virulent than its parent Ab4 virus. Here, we describe the Ab4 challenge infection evaluating protection induced by the Ab4ΔORF1/71 vaccine candidate. Susceptible control horses developed respiratory disease, fever, nasal shedding, and viremia. Full protection after challenge infection was observed in 5/5 previously Ab4 infected horses and 3/5 Ab4ΔORF1/71 horses. Two Ab4ΔORF1/71 horses developed short-lasting viremia and/or virus shedding. Protective immunity in the respiratory tract was characterized by pre-existing EHV-1-specific IgG4/7 antibodies, the absence of IFN-α secretion and rapidly increasing IgG4/7 upon challenge infection. Pre-existing systemic EHV-1-specific IgG4/7 highly correlated with protection. T-cell immunity was overall low. In conclusion, protective immunity against EHV-1 infection including prevention of viremia was associated with robust systemic and intranasal IgG4/7 antibodies suggesting immediate virus neutralization at the local site.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Publication Date: 2019-03-22 PubMed ID: 30928700DOI: 10.1016/j.virol.2019.03.014Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The research focuses on the efficacy of a potential vaccine candidate for Equid herpesvirus-1 (EHV-1) in horses. The vaccine candidate is shown to reduce symptoms of EHV-1 infection including respiratory disease, fever, nasal shedding, and viremia.
Background and Aim of the Study
- Equid herpesvirus-1 is a significant infectious disease in horses that causes outbreaks frequently. The disease leads to respiratory problems, fever, nasal shedding, and viremia, a condition in which the virus enters the bloodstream and spreads throughout the body.
- Despite the use of vaccines, the control of EHV-1 outbreaks remains a challenge. The aim of this study was to develop and test a new potential vaccine candidate, Ab4ΔORF1/71, to fight against EHV-1 infection.
Methodology and Findings
- The researchers had previously shown that a gene deletion mutant of the EHV-1 strain Ab4 (Ab4ΔORF1/71) was less virulent than its parent virus Ab4. In this study, they test the protective effects of this mutant virus as a vaccine candidate.
- The Ab4ΔORF1/71 vaccine candidate was administered to susceptible horses and then these horses were exposed to the Ab4 challenge infection.
- The results showed that susceptible control horses developed the typical symptoms of EHV-1 infection. However, horses that had been vaccinated with Ab4ΔORF1/71 demonstrated full protection in 3 out of 5 cases. The remaining two vaccinated horses exhibited short-lived viremia and/or virus shedding.
Interpretation and Conclusion
- The protective immunity against EHV-1 infection in the respiratory tract was found to be associated with the pre-existence of EHV-1-specific IgG4/7 antibodies. These antibodies increased rapidly upon challenge infection.
- Additionally, the horses which were protected did not show IFN-α secretion, and there was a high correlation between pre-existing systemic EHV-1-specific IgG4/7 antibodies and protection. This suggests that the antibodies played a primary role in immunity.
- Surprisingly, T-cell immunity, a crucial aspect of the immune response, was found to be overall low in this study.
- In conclusion, the research indicates that robust systemic and intranasal IgG4/7 antibodies may provide significant protection against EHV-1 infection, potentially neutralizing the virus at the site of infection, therefore making the Ab4ΔORF1/71 a promising vaccine candidate for further evaluations.
Cite This Article
APA
Perkins G, Babasyan S, Stout AE, Freer H, Rollins A, Wimer CL, Wagner B.
(2019).
Intranasal IgG4/7 antibody responses protect horses against equid herpesvirus-1 (EHV-1) infection including nasal virus shedding and cell-associated viremia.
Virology, 531, 219-232.
https://doi.org/10.1016/j.virol.2019.03.014 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: gap7@cornell.edu.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: sb687@cornell.edu.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: aek68@cornell.edu.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: hss23@cornell.edu.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: am89@cornell.edu.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: clwimer1@yohoo.com.
- Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States. Electronic address: bw73@cornell.edu.
MeSH Terms
- Administration, Intranasal
- Animals
- Antibodies, Viral / immunology
- Female
- Herpesviridae Infections / immunology
- Herpesviridae Infections / prevention & control
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / drug effects
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / physiology
- Herpesvirus Vaccines / administration & dosage
- Herpesvirus Vaccines / immunology
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horse Diseases / virology
- Horses
- Immunoglobulin G / immunology
- Male
- Nasal Mucosa / immunology
- Nasal Mucosa / virology
- Vaccination
- Viremia / immunology
- Viremia / prevention & control
- Viremia / veterinary
- Viremia / virology
- Virus Shedding
Citations
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