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Home / Equine Research Bank / J Virol / An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame ...
Journal of virology2019; 93(22); e01011-19; doi: 10.1128/JVI.01011-19

An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and Disease.

Abstract: Equine herpesvirus type 1 (EHV-1) outbreaks continue to occur despite widely used vaccination. Therefore, development of EHV-1 vaccines providing improved immunity and protection is ongoing. Here, an open reading frame 2 deletion mutant of the neuropathogenic EHV-1 strain Ab4 (Ab4ΔORF2) was tested as a vaccine candidate. Three groups of horses ( = 8 each) were infected intranasally with Ab4ΔORF2 or the parent Ab4 virus or were kept as noninfected controls. Horses infected with Ab4ΔORF2 had reduced fever and nasal virus shedding compared to those infected with Ab4 but mounted similar adaptive immunity dominated by antibody responses. Nine months after the initial infection, all horses were challenged intranasally with Ab4. Previously noninfected horses (control/Ab4) displayed clinical signs, shed large amounts of virus, and developed cell-associated viremia. In contrast, 5/8 or 3/8 horses previously infected with Ab4ΔORF2 or Ab4, respectively, were fully protected from challenge infection as indicated by the absence of fever, clinical disease, nasal virus shedding, and viremia. All of these outcomes were significantly reduced in the remaining, partially protected 3/8 (Ab4ΔORF2/Ab4) and 5/8 (Ab4/Ab4) horses. Protected horses had EHV-1-specific IgG4/7 antibodies prior to challenge infection, and intranasal antibodies increased rapidly postchallenge. Intranasal inflammatory markers were not detectable in protected horses but quickly increased in control/Ab4 horses during the first week after infection. Overall, our data suggest that preexisting nasal IgG4/7 antibodies neutralize EHV-1, prevent viral entry, and thereby protect from disease, viral shedding, and cell-associated viremia. In conclusion, improved protection from challenge infection emphasizes further evaluation of Ab4ΔORF2 as a vaccine candidate. Nasal equine herpesvirus type 1 (EHV-1) shedding is essential for virus transmission during outbreaks. Cell-associated viremia is a prerequisite for the most severe disease outcomes, abortion and equine herpesvirus myeloencephalopathy (EHM). Thus, protection from viremia is considered essential for preventing EHM. Ab4ΔORF2 vaccination prevented EHV-1 challenge virus replication in the upper respiratory tract in fully protected horses. Consequently, these neither shed virus nor developed cell-associated viremia. Protection from virus shedding and viremia during challenge infection in combination with reduced virulence at the time of vaccination emphasizes ORF2 deletion as a promising modification for generating an improved EHV-1 vaccine. During this challenge infection, full protection was linked to preexisting local and systemic EHV-1-specific antibodies combined with rapidly increasing intranasal IgG4/7 antibodies and lack of nasal type I interferon and chemokine induction. These host immune parameters may constitute markers of protection against EHV-1 and be utilized as indicators for improved vaccine development and informed vaccination strategies.
Copyright © 2019 American Society for Microbiology.
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Publication Date: 2019-10-29 PubMed ID: 31462575PubMed Central: PMC6819910DOI: 10.1128/JVI.01011-19Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the development and testing of a new vaccine against Equine herpesvirus type 1 (EHV-1), which is a major cause of disease in horses. The vaccine, developed from a mutated form of the virus, showed potential in protecting horses from the virus, highlighting its potential for further evaluation and development.

Study Objectives and Method

  • The main objective of this study is to develop and evaluate a new vaccine, specifically an open reading frame 2 deletion mutant, of the neuropathogenic EHV-1 strain Ab4 (referred to as Ab4ΔORF2).
  • As part of the study, three groups of horses, eight in each, were used. One group was infected with the vaccine candidate Ab4ΔORF2, the second group with the parent Ab4 virus and the third group was kept as non-infected controls.

Results and Observations

  • The study found that horses infected with the vaccine showed reduced fever and nasal virus shedding, the excretion of virus particles, compared to those infected with the parent strain.
  • After nine months, all horses were given a challenge infection with the Ab4 virus. Most of the horses previously infected with the vaccine were fully protected from the challenge infection, displaying no symptoms and shedding no virus.
  • The horses that had been given the vaccine also showed specific immunoglobulin G (IgG) antibodies against the virus and did not display any inflammation, unlike the control group.

Interpretation and Significance

  • The presence of IgG antibodies in horses infected with the vaccine candidate suggests that the vaccine was able to induce an immune response in the horses, therefore offering protection against the virus.
  • The follow-up infection conducted nine months later indicated that this immunity persisted over time, showing the potential of the vaccine to provide long-lasting protection against EHV-1.
  • The lack of disease symptoms, viral shedding and cell-associated viremia (the presence of viruses in the blood) in vaccinated horses emphasizes the promise of the Ab4ΔORF2 vaccine candidate.
  • The discovery of local and systemic EHV-1-specific antibodies along with rapidly increasing intranasal IgG antibodies and lack of nasal type I interferon and chemokine induction could be potentially be used as indicators of protection against EHV-1, guiding the development of improved vaccine formulations and strategies.

To summarise, the research presents insights into an improved vaccine candidate for EHV-1 in horses, and suggests potential biomarkers for vaccine efficacy and protection. This could guide future efforts in equine vaccine development and strategies to prevent EHV-1 transmission and disease.

Cite This Article

APA
Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. (2019). 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, 93(22), e01011-19. https://doi.org/10.1128/JVI.01011-19

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 93
Issue: 22
PII: e01011-19

Researcher Affiliations

Schnabel, Christiane L
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Babasyan, Susanna
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Rollins, Alicia
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Freer, Heather
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Wimer, Christine L
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Perkins, Gillian A
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Raza, Fahad
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Osterrieder, Nikolaus
  • Institut für Virologie, Freie Universität Berlin, Berlin, Germany.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA bw73@cornell.edu.

MeSH Terms

  • Administration, Intranasal / methods
  • Animals
  • Antibodies, Viral
  • Female
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Equid / genetics
  • Herpesvirus 1, Equid / immunology
  • Herpesvirus 1, Equid / metabolism
  • Herpesvirus Vaccines / immunology
  • Horse Diseases / virology
  • Horses
  • Male
  • Nasal Mucosa / virology
  • Open Reading Frames
  • Rhadinovirus / immunology
  • Vaccination / veterinary
  • Viremia / immunology
  • Virulence
  • Virus Shedding / immunology

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Citations

This article has been cited 18 times.
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