A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.
Abstract: Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection-the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert I.N. (Flu Avert), which is known to stimulate strong antiviral responses, will enhance antiviral innate immunity, and that these responses would also provide protection from EHV-1 infection. To test our hypothesis, primary equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and innate immunity was evaluated for 10 days following treatment. The timing of Flu Avert treatment was also evaluated for optimal effectiveness to reduce EHV-1 replication by modulating early immune responses to EHV-1. The induction of interferons, cytokine and chemokine mRNA expression, and protein secretion was evaluated by high-throughput qPCR and multiplex protein analysis. Intracellular and extracellular EHV-1 titers were determined by qPCR. Flu Avert treatment resulted in the modulation of IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment. Coinciding with the timing of optimal chemokine induction, our data also suggested the same timing for reduction of EHV-1 replication. In combination, our results suggest that Flu Avert may be effective at counteracting some of the immune-modulatory properties of EHV-1 at the airway epithelium and the peak for this response occurs 5-8 days post-Flu Avert treatment. Future studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.
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The research is about how a vaccine for equine influenza, Flu Avert I.N., could potentially provide protection against equine herpesvirus 1 (EHV-1) by stimulating the horse’s innate immunity.
Research Context
Equine herpesvirus 1 (EHV-1) is a ubiquitous virus that infects horses globally, causing respiratory disease, abortion, and a condition known as equine herpesvirus myeloencephalopathy.
Developing protection against EHV-1 is difficult because the virus establishes latency and have features that modulate the immune response of the horse.
The study hypothesizes that a mucosal influenza vaccine named Flu Avert, known for its strong antiviral responses, could potentiate the innate immune response and offer protection from EHV-1 infection.
Research Process
Equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and the innate immunity changes were observed for 10 days following treatment.
The effectiveness of the Flu Avert treatment and its timing in reducing EHV-1 replication was evaluated, with the focus on early immune responses to the EHV-1 virus.
Tools such as high-throughput qPCR and multiplex protein analysis were used to evaluate the induction of interferons, cytokine and chemokine mRNA expression, and protein secretion.
Intracellular and extracellular EHV-1 titers, which measure the amount of the virus, were determined through PCR.
Findings
Flu Avert treatment modulated cytokines like IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment.
The timing of optimal chemokine induction and the reduction in EHV-1 replication seemed to coincide, suggesting that Flu Avert could be most effective against EHV-1 when administered 5-8 days before potential exposure.
Therefore, the study indicates that Flu Avert may be capable of counteracting some of EHV-1’s immune-modulatory properties at the airway epithelium.
Implications for Future Research
The results suggest there could be potential for using Flu Avert as a prophylactic in situations where EHV-1 exposure might occur.
Further studies are needed to fully understand the potential of Flu Avert in reducing the impacts of EHV-1.
Cite This Article
APA
Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G.
(2021).
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, 8, 674850.
https://doi.org/10.3389/fvets.2021.674850
Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Veterinary Medical Center, East Lansing, MI, United States.
Vaala, Wendy E
Merck & Co., Inc., Kenilworth, NJ, United States.
Barnett, D Craig
Merck & Co., Inc., Kenilworth, NJ, United States.
Bain, Fairfield T
Merck & Co., Inc., Kenilworth, NJ, United States.
Soboll Hussey, Gisela
Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Veterinary Medical Center, East Lansing, MI, United States.
Conflict of Interest Statement
WV, DB, and FB are employed by MSD Animal Health. 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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