Immune responses to commercial equine vaccines against equine herpesvirus-1, equine influenza virus, eastern equine encephalomyelitis, and tetanus

ABSTRACT Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2–EHV-1–gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2–EHV-1–gD vaccine and the commercially available vaccine Vetera EHVXP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals (P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2–EHV-1–gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations (P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge (P < 0.01 or P < 0.05). Vaccination with VC2–EHV-1–gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4+ T cells and CD8+ T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus-vectored VC2–EHV-1–gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.

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Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge

Journal of Virology ◽

10.1128/jvi.00986-16 ◽

2016 ◽

Vol 90 (18) ◽

pp. 8090-8104 ◽

Cited By ~ 3

Author(s):

Seong K. Kim ◽

Akhalesh K. Shakya ◽

Dennis J. O'Callaghan

Keyword(s):

Immune Responses ◽

Alveolar Macrophages ◽

Innate Immune ◽

Equine Herpesvirus ◽

Innate Immune Responses ◽

Lethal Challenge ◽

Equine Herpesvirus 1 ◽

Interferon Stimulated Genes ◽

Ifn Γ ◽

Herpesvirus 1

ABSTRACTEquine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammation of the lung, causing infected mice to succumb at 4 to 6 days postinfection. Our previous results showed that KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks postimmunization and that KyA infection elicited protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of innate immune responses to KyA, KyA-immunized mice were challenged with RacL11 at various times postvaccination. KyA immunization protected mice from RacL11 challenge at 1 to 7 days postimmunization. Immunized mice lost less than 10% of their body weight and rapidly regained weight. Virus titers in the lungs of KyA-immunized mice were 1,000-fold lower at 2 days post-RacL11 challenge than virus titers in the lungs of nonimmunized mice, indicating accelerated virus clearance. Affymetrix microarray analysis revealed that gamma interferon (IFN-γ) and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γ inhibited EHV-1 infection of murine alveolar macrophages and protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression is important in mediating the protection elicited by KyA immunization. These results suggest that EHV-1 KyA may be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.IMPORTANCEViral infection of cells initiates a signal cascade of events that ultimately attempts to limit viral replication and prevent infection through the expression of host antiviral proteins. In this study, we show that EHV-1 KyA immunization effectively protected CBA mice from pathogenic RacL11 challenge at 1 to 7 days postvaccination and increased the expression of IFN-γ and 16 antiviral interferon-stimulated genes (ISGs). The administration of IFN-γ blocked EHV-1 replication in murine alveolar macrophages and mouse lungs and protected mice from lethal challenge. To our knowledge, this is the first report of an attenuated EHV-1 vaccine that protects the animal at 1 to 7 days postimmunization by innate immune responses. Our findings suggested that IFN-γ serves as a novel prophylactic agent and may offer new strategies for the development of anti-EHV-1 agents in the equine.

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Equine Herpesvirus-1 Interferes with Type-I IFN-Mediated Immune Responses in vitro in Equine Endothelial Cells

Journal of Equine Veterinary Science ◽

10.1016/j.jevs.2016.02.145 ◽

2016 ◽

Vol 39 ◽

pp. S67

Author(s):

S. Sarkar ◽

U.B.R. Balasuriya ◽

D.W. Horohov ◽

T.M. Chambers

Keyword(s):

Endothelial Cells ◽

Immune Responses ◽

Type I ◽

Equine Herpesvirus ◽

Type I Ifn ◽

Equine Herpesvirus 1 ◽

Herpesvirus 1

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Trials For Preparation Of Combined Vaccine Of Equine Influenza, Equine Herpesvirus–1, Rabies Virus And Tetanus Toxoid

Journal of Applied Veterinary Sciences ◽

10.21608/javs.2021.140096 ◽

2021 ◽

Vol 6 (1) ◽

pp. 38-44

Author(s):

Safaa A. Warda ◽

wafaa abdelaziz ◽

Eman M. Ebied ◽

Nashwa K. Madkour ◽

Hala El Sawy ◽

...

Keyword(s):

Rabies Virus ◽

Tetanus Toxoid ◽

Equine Herpesvirus ◽

Equine Herpesvirus 1 ◽

Equine Influenza ◽

Herpesvirus 1 ◽

Combined Vaccine

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A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.674850 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lila M. Zarski ◽

Wendy E. Vaala ◽

D. Craig Barnett ◽

Fairfield T. Bain ◽

Gisela Soboll Hussey

Keyword(s):

Innate Immunity ◽

Influenza Vaccine ◽

Equine Herpesvirus ◽

Equine Herpesvirus 1 ◽

Equine Influenza ◽

Antiviral Responses ◽

Herpesvirus 1 ◽

Antiviral Innate Immunity ◽

Respiratory Epithelial

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 in vivo studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.

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