EHV-1: Current Vaccines, Challenges, & Future Directions

This article originally appeared in the Spring 2025 issue of EquiManagement. Sign up here for a FREE subscription to EquiManagement’s quarterly digital or print magazine and any special issues.

Equine herpesvirus-1 (EHV-1) and equine herpesvirus myeloencephalopathy (EHM) have huge economic impacts on the equine industry besides expensive and tragic cases treating affected horses. When outbreaks occur, owners worry their horses might contract EHM, events get canceled, and quarantine measures must be implemented. About 10% of horses infected with EHV-1 develop neurologic disease from EHM. With this in mind, researchers are trying to develop vaccines that protect beyond the respiratory form to mitigate EHM and possibly abortion.

Gisela Soboll Hussey, DVM, MS, PhD, Professor of Pathology and Diagnostics at the Michigan State College of Veterinary Medicine, recently discussed updated research in this vaccine field during a presentation at the University of Kentucky’s Gluck Equine Research Center.

Currently, EHV-1 vaccines supplement hygiene and biosecurity strategies—­cornerstone measures of EHV-1 control. There is no evidence that the available EHV-1 vaccines fully protect against viremia or prevent EHM. Soboll Hussey noted two host risk factors of particular interest:

• For horses younger than 15 years of age, only 10% develop EHM.
• Horses older than 20 years have a 50-70% risk of developing EHM.

She explained that there is no reliable EHM model to identify immune correlates for protection from EHM and test potential vaccine candidates. So, researchers must rely on in vivo models of endothelial cell infection. In an ocular model, the chorioretinal endothelium is infected in a similar manner as the equine spinal cord. Lesions of “holes punched” into the tapetal fundus only begin to show in more chronic cases in 50% of infected horses. A different approach using a ­proteomic/metabolomic model lacks direct correlation of biomarkers with EHM.

EHM in Young vs. Old Horses

Because the immune system of younger horses is more capable of controlling EHM, Soboll Hussey said there is value in comparing young and old horses infected with the neuropathogenic strain to identify host factors. In one study, researchers examined clinical disease of both respiratory and neurologic signs, nasal viral shedding, and viremia to compare immune responses and postmortem results. She described the findings:

• Old horses do not have a primary fever, while young horses exhibit the classic biphasic fever around Days 2 and 6. 
• Young horses develop significant respiratory disease, while old horses do not.
• In the second week of infection, 9/9 old horses showed neurologic signs compared to 1/9 young horses. 
• The one young neurologic horse and 3/9 neurologic old horses recovered.

Immune Responses in Different Body Sites

Of significance, nasal viral shedding decreased and viremia increased in old and EHM horses. Different body sites have different immune responses:

• In respiratory nasal secretions, IFN-α and IL-17 (interleukin-17) upregulated in non-EHM horses, whereas IL-10 increased in EHM horses.
• An interferon response initiates early in non-EHM horses and during viremia in EHM horses. In other words, the interferon response in old horses delays until the start of viremia.
• TH-1 helper-cell-associated cytokines upregulate in non-EHM horses.
• EHM horses had dysregulation and impairment of T-cell response.
• In cerebral spinal fluid before infection occurs, IL-10 was elevated in 8/10 horses that developed EHM.
• EHM horses had high serum IgG 3/5.

In summary, Soboll Hussey stated, “Immune responses show no activation of TH-2 immunity (which activates B cells and antibodies) in the respiratory epithelium; instead, there is increased IL-10. During viremia early on, there is a delayed response and reduced activation of interferon and Tbet (immune cell transcription factor that drives development of TH-1 helper cells). And, the horses that develop EHM show increased IgG 3/5 and decreased pCTL (cytotoxic T lymphocytes) pre-infection. The type of immunity needed to protect against EHM is predisposed to be more of a TH-2 regulatory immunity rather than a cellular response.”

If we could modify the IL-10 response to instead respond with interferon, it would induce TH-1, CTLs, and IgG 4/7 rather than IgG 3/5. Certain genes also play a role; for example, ORF ½ genes modulate cytokine responses and attenuate clinical disease, nasal shedding, and viremia. Soboll Hussey’s genetic research shows little induction of immunity following primary intranasal infection. The ORF ½ deletion did little to attenuate clinical disease but did restore IL-8 and Tbet and increased induction of type 1 interferon responses while decreasing IL-10 response.

Inducing Protective Immunity Against EHV-1

They also looked at the use of nucleic acid technology (mRNA and self-­amplifying mRNA vaccines) to induce protective immunity. It targets the lymph nodes rather than the respiratory tract. The human shingles infection is in the same family as equine EHV-1 and -4, and the Shingrix vaccine “shows remarkable protection from shingles in older and immunocompromised humans.”  

In a study trial, researchers screened equine vaccine candidates for safety and immunogenicity using two doses of ­Shingrix-like vaccine at a high (250 ug) and low (100 ug) dose; controls were vaccinated with the spike from COVID-19 virus. The first vaccine elicited the most response. They assessed cellular immunity four months after the second vaccine and found a notable delayed-type skin reaction (wheal) useful for measuring the intradermal response from inactivated EHV-1 virus. The test horses had strong antibody responses and induction of CTL antigens. 

Research is ongoing, but scientists now have an option that could yield promising results for protection against EHM. 

Related Reading

• Kester News Hour Hot Topics: Melanoma, EHV-1, and Lyme Disease
• Is Vaccination Against Equine Herpesvirus Type 1 (EHV-1) a Rational Choice?
• Disease Du Jour: Equine Herpesvirus Refresher

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