While there are several vaccines available for protection against both respiratory and abortogenic forms of EHV-1, at this time there is no equine vaccine that has a label claim for protection against the neurological strain of the virus. Consult your veterinarian for further guidance if you are considering the use of EHV-1 vaccines.

Discussion of EHV-1 Vaccination for Veterinary Professionals

Vaccination for Equine Herpesvirus-1 Myeloencephalopathy: The Dilemma
By W. David Wilson BVMS, MS
The goal of vaccination is to induce resistance to infection and disease by eliciting a strong and durable immune response without inducing clinical signs of disease in the vaccinated animal. Traditionally, this has been accomplished by altering disease-causing infectious organisms so that they no longer cause disease but retain the antigens necessary for inducing a protective immune response.

Until recently, only two types of vaccines have been available for use in horses and other animals. These include inactivated (killed) vaccines containing "dead" organisms, and attenuated or modified live vaccines (MLV) containing living organisms that have been attenuated in virulence so that they multiply in the host after administration but do not cause disease. While the introduction of West Nile virus infection into North America in 1999 has resulted in devastating consequences to the horse, human and bird populations of many states, it has also spurred the development and licensing of advanced vaccine technologies-including recombinant vectored, chimera, and DNA vaccines-that will greatly benefit equine health in the future.

The ideal vaccine would completely block infection by inducing so-called sterile immunity. In this instance, not only is clinical disease prevented when the vaccinated animal is exposed to the infectious agent, but shedding of that virus or bacterium by the vaccinated animal is also prevented, and the animal's potential to act as a source of contagion to infect other animals is eliminated.

In reality, few vaccines accomplish this goal. They may prevent development of clinical disease or at least reduce the severity of signs associated with infection by limiting multiplication of the infectious agent in the vaccinated animal. In turn, shedding of the infectious agent by the vaccinated animal is reduced but not eliminated so that the potential to transmit infection to other animals remains.

For most diseases, the best vaccines stimulate immune responses that closely mimic those that result from recovery from natural infection. Thus, the maximum possible degree and duration of protection induced by a particular vaccine can usually be predicted based on the effectiveness of the immune response resulting from natural infection. It is unreasonable to expect traditional MLV or inactivated vaccines to induce immunity that is stronger than that resulting from recovery from field infection.

In the case of EHV-1 and many other herpesviruses, resistance to re-infection resulting from recovery from field infection is short-lived, lasting only a few weeks to a few months. EHV-1 infects the horse through the respiratory tract and rapidly becomes internalized by cells, including circulating lymphocytes. It is then passed directly from cell to cell without an extracellular phase during which the virus could otherwise be exposed to neutralizing antibodies and other immune effectors. As such, EHV-1 vaccines would need to satisfy a challenging set of demands in order to be highly effective.

The ideal EHV-1 vaccine would not only be safe and lend itself to efficient delivery, it would also invoke strong and persistent local humoral (virus-neutralizing antibody) and cellular (cytotoxic T-lymphocyte, CTL) responses at the level of the mucosal lining of the respiratory tract in order to block infection. In addition, it would induce durable systemic humoral and CTL responses to rapidly clear free virus and destroy virus-infected cells in the event that the mucosal response was not successful in blocking infection. Beyond that, the ideal vaccine would be capable of inducing this broad spectrum of immune responses in foals at a young age to protect them against the field challenge that inevitably occurs during the first year or two of life and leads to a chronic latent-carrier state.

Currently Available EHV-1 Vaccines

Commercially available vaccines currently include two single-component inactivated vaccines (Pneumabort K and Prodigy) marketed for the prevention of EHV-1-induced abortion in pregnant mares; several multicomponent inactivated vaccines (Prestige, Calvenza, Innovator); and one MLV vaccine (Rhinomune) marketed for prevention of respiratory disease induced by EHV-1 and EHV-4. All are administered by intramuscular injection. Each of these vaccines induce some but not all of the desired components of the immune response. None induces sterile immunity or complete protection from clinical disease. The best that can be hoped for is a reduction in the severity of clinical signs and in the amount of EHV-1 shed by vaccinated horses that do become infected, which in turn may reduce the incidence of disease within the herd or group.

Prospects of Vaccinating to Prevent EHV-1 Myeloencephalopathy

Frequent revaccination of mature horses to prevent EHV-1 myeloencephalopathy is not clearly justified in most circumstances for the following reasons:

• Most mature horses have been infected previously with EHV-1 and are latent carriers of the virus.
• EHV-1 myeloencephalopathy is a relatively rare disease from a population standpoint.
• Currently available vaccines do not reliably block infection or claim to prevent myeloencephalopathy.
• EHV-1 myeloencephalopathy has been observed in horses vaccinated against EHV-1 regularly at 3- to 4-month intervals.
• Vaccination has been cited by some as a potential risk factor for development of myeloencephalopathy.

On the other hand, regular revaccination of pregnant mares and other horses on breeding farms to reduce the risk of EHV-1-induced abortion is strongly recommended.

An Issue with Difficult Pros and Cons

In the wake of recent outbreaks of EHV-1 myeloencephalopathy in diverse populations of horses in several regions of North America, many racing jurisdictions and managers of equine facilities and events have imposed EHV-1 vaccination requirements for incoming and resident horses in the hope that manifestations of EHV-1 infection, particularly EHV-1 myeloencephalopathy and the febrile phase that typically precedes the onset of neurological signs, can be prevented.

The efficacy of this approach remains to be proven. However, there is little doubt that enforcement of strict biosecurity measures and hygiene practices are likely to be more effective than widespread vaccination in reducing the risk of acquiring infection. Nevertheless, recent research demonstrates that viral shedding is much reduced in horses with high circulating titers of virus-neutralizing (VN) antibody, as well as in horses that have been vaccinated recently with the Rhinomune MLV vaccine. Of the available inactivated vaccines, Calvenza and both vaccines marketed for prevention of abortion (Pneumabort K and Prodigy) contain the highest amounts of antigen and stimulate the highest levels of VN antibody.

On premises with confirmed clinical EHV-1 infection (myeloencephalopathy, fever, respiratory disease, or abortion), booster vaccination of horses that are likely to have been exposed already is not recommended. However, it seems rational to booster-vaccinate nonexposed horses and horses that must enter the premises with one of the four vaccines listed above (i.e., Rhinomune, Calvenza, Pneumabort K, or Prodigy) if the horses have not been vaccinated against EHV-1 within the previous 90 days. This approach relies on the reasonable assumption that the immune system of most mature horses has already been "primed" by prior exposure to EHV-1 antigens through field infection or vaccination and can, therefore, be "boosted" within 7 to 10 days of administration of a single dose of EHV-1 vaccine.

While this approach by no means guarantees protection of individual horses against the potentially fatal neurological consequences of EHV-1 infection, the hope is that reduced nasal shedding of infectious EHV-1 by recently vaccinated horses will indirectly help protect other horses by reducing the dose of virus to which they are exposed.

A recent publication described a study in which 5 Rhinomune-vaccinated horses, 5 horses vaccinated with an inactivated multicomponent respiratory EHV-1 vaccine, and 5 nonvaccinated control horses were all challenged with the Findlay '03 neuropathogenic strain of EHV-1 by nasal spray. The results of this study provided preliminary evidence that recent vaccination with Rhinomune may provide some protection against EHV-1 myeloencephalopathy. Similarly, a study published in 1978 by the manufacturers of Pneumabort K to test the effectiveness of this vaccine in preventing abortion provided tentative evidence for induction of at least partial protection against EHV-1 myeloencephalopathy.

While results of these studies are encouraging, they should be interpreted with caution because of the relatively small number of horses used, the difficulty that researchers have experienced in the past in designing a challenge model that produces consistent results, and the knowledge that in the field, high morbidity outbreaks of EHM have been encountered in regularly vaccinated horses. Undoubtedly, further research is needed before definitive conclusions can be drawn.

Summary of EHV-1 Vaccination Dilemma

• Current EHV-1 vaccines do not prevent primary infection or establishment of the latent carrier state.
• Maternally derived antibodies interfere with the response of most foals to vaccination with inactivated and MLV vaccines until foals are 5 months of age, and likely older in some cases. If we wait until 5 months or older to start vaccinating foals, many (or most) will encounter field challenge, become infected with or without clinical signs (nasal discharge, cough, fever), and fail to clear the virus, thereby establishing a chronic latent carrier state. This problem applies to both EHV-1 and EHV-4. The introduction and widespread use of EHV vaccines on stud farms in Australia in recent years has failed to reduce the incidence of EHV-1 and EHV-4 infection and disease in foals, weanlings and yearlings.
• Available vaccines do not reliably prevent infection, even when they induce high antibody titers. They do, however, variously accomplish (a) a reduction in (non-neurologic) clinical signs after challenge in the experimental setting, at least when challenge is performed within a few weeks following vaccination, and (b) reduced viral shedding from the respiratory tract after challenge, thereby helping reduce the magnitude of challenge experienced by other horses and potentially helping reduce spread to minimize outbreaks. The latter point makes sense from a clinical standpoint but has not been proven in either the field or experimental setting.
• Most mature horses are latent carriers of EHV-1 and EHV-4. Therefore, most of the horses to which vaccines are administered are already latently infected.
• Available vaccines do not claim to prevent EHV-1 myeloencephalopathy.
• The incidence of EHV-1 myeloencephalopathy seems to be increasing in both North America and Europe, in countries that vaccinate against EHV-1/4 regularly, as well as in countries such as Holland, where EHV vaccines are rarely used.
• EHV-1 myeloencephalopathy has been encountered in horses vaccinated regularly at 3- to 5-month intervals.
• Pregnant mares appear to be at increased risk of developing EHV-1 myeloencephalopathy, even though this is the population of horses that is most intensively vaccinated against EHV-1.
• Vaccination has been cited as a risk factor for development of EHV-1 myeloencephalopathy in one (unpublished) paper written to report on an outbreak in 1984 involving many horses on at least five premises in Southern California.
• The paper reporting the 2003 outbreak at the University of Findlay showed a strong trend toward increased risk of developing EHV-1 myeloencephalopathy in frequently vaccinated horses. However, this result was likely confounded by the finding that horses more than 5 years of age were at increased risk of developing neurological disease compared with younger horses. The older horses in the Findlay outbreak were also the ones that were vaccinated most frequently against EHV-1. This age-associated risk has been documented in other studies.