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Development of a live attenuated vaccine candidate for equid alphaherpesvirus 1 control: a step towards efficient protection.
Abstract: Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as a molecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied and then in an experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and ΔUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the ΔgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and ΔUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the ΔUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the ΔUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection.
Copyright © 2024 Hu, Wu, Jia, Zhang, Sun, Sa, Zhang, Cai, Jarhen, Ran and Liu.
Publication Date: 2024-07-03 PubMed ID: 39021566PubMed Central: PMC11252532DOI: 10.3389/fimmu.2024.1408510Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
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.
Overview
- This study focuses on developing a live attenuated vaccine candidate for Equid alphaherpesvirus 1 (EqAHV1), a virus that causes respiratory, neurological, and reproductive issues in horses.
- The researchers engineered mutant viruses with specific gene deletions and tested their safety, viral growth, and ability to elicit immune protection, identifying a promising vaccine candidate.
Background and Importance
- Equid alphaherpesvirus 1 (EqAHV1): A significant viral pathogen in horses responsible for respiratory disease, neurological syndromes, and abortion storms.
- Current Vaccine Situation: Existing vaccines do not provide complete protection, and there is no licensed vaccine that utilizes marker strategies to allow Differentiation of Infected and Vaccinated Animals (DIVA).
- DIVA Concept: Marker vaccines incorporate molecular markers to distinguish vaccinated animals from infected ones, which is critical for controlling outbreaks effectively.
Key Molecular Targets in Virus Engineering
- Glycoprotein 2 (gp2): A viral envelope protein with high antigenicity that serves as a molecular marker suitable for the DIVA approach.
- Virulence Genes Deleted: Thymidine kinase (TK), UL24 (a gene involved in viral replication), and glycoproteins gI/gE also targeted for deletion to attenuate the virus.
Experimental Design
- Engineered several mutant strains of EqAHV1 with deletions in gp2 alone or combined with other virulence genes:
- Δgp2
- ΔTK/gp2
- ΔUL24/TK/gp2
- ΔgI/gE/gp2
- Compared these mutants against the wild-type (WT) virus in terms of viral growth and pathogenicity in vitro and in an in vivo hamster model.
Key Findings: Viral Growth and Pathogenicity
- In RK-13 cell cultures:
- Δgp2, ΔTK/gp2, and ΔUL24/TK/gp2 strains showed reduced viral growth compared to WT.
- ΔgI/gE/gp2 strain had severely impaired proliferation.
- In Golden Syrian hamsters:
- The Δgp2 virus still caused clinical symptoms and mortality, indicating incomplete attenuation.
- ΔTK/gp2 and ΔUL24/TK/gp2 mutants showed significantly reduced pathogenicity, causing no symptoms or fatalities.
Immune Response and Vaccine Efficacy
- Nasal immunization with vaccines containing ΔTK/gp2 and ΔUL24/TK/gp2 mutants induced robust immune responses in hamsters.
- Between the two, the vaccine with the ΔUL24/TK/gp2 strain provided stronger immune protection upon WT challenge.
DIVA Strategy Development
- Established and optimized an ELISA test targeting gp2 glycoprotein to differentiate infected from vaccinated animals.
- This is valuable for outbreak control and epidemiological surveillance by identifying vaccination status and natural infection.
Conclusions and Implications
- The ΔUL24/TK/gp2 strain is a promising live attenuated vaccine candidate that balances safety and efficacy against EqAHV1.
- Its use as a nasal vaccine could provide effective protection while enabling DIVA-compatible surveillance.
- This work represents a significant step toward efficient prevention and control of EqAHV1 outbreaks in equine populations.
Cite This Article
APA
Hu Y, Wu G, Jia Q, Zhang B, Sun W, Sa R, Zhang S, Cai W, Jarhen , Ran D, Liu J.
(2024).
Development of a live attenuated vaccine candidate for equid alphaherpesvirus 1 control: a step towards efficient protection.
Front Immunol, 15, 1408510.
https://doi.org/10.3389/fimmu.2024.1408510 Publication
Researcher Affiliations
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
- Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
- Preventive Control Section, Aksu Regional Animal Disease Control and Diagnostic Center, Aksu, Xinjiang Uygur Autonomous Region, China.
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
- Chinese Academy of Sciences (CAS) Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China.
- Food, Agricultural and Health Products Division, Centre Testing International Group Co., Ltd., Qingdao, Shandong, China.
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
- Product Manufacturing Sector, GemPharmatech Co., Ltd., Shanghai, China.
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
- Laboratory of Animal Infectious Disease, College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi, Xinjiang Uygur Autonomous Region, China.
MeSH Terms
- Animals
- Vaccines, Attenuated / immunology
- Herpesviridae Infections / prevention & control
- Herpesviridae Infections / immunology
- Herpesviridae Infections / virology
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / genetics
- Horses
- Mesocricetus
- Antibodies, Viral / blood
- Antibodies, Viral / immunology
- Viral Envelope Proteins / immunology
- Viral Envelope Proteins / genetics
- Cricetinae
- Horse Diseases / prevention & control
- Horse Diseases / immunology
- Horse Diseases / virology
- Viral Vaccines / immunology
- Viral Vaccines / genetics
- Cell Line
- Mutation
Conflict of Interest Statement
Author WS is employed by Centre Testing International Group Co., Ltd. Author WC is employed by GemPharmatech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Citations
This article has been cited 2 times.- Kutumbetov L, Myrzakhmetova B, Tussipova A, Zhapparova G, Tlenchiyeva T, Bissenbayeva K, Nurabayev S, Kerimbayev A. Development and Preclinical Evaluation of a Lyophilized Vaccine Against Equine Herpesvirus Type 4 (EHV-4). Vaccines (Basel) 2025 May 31;13(6).
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