Equine vaccination recommendations: what now? (Proceedings)

Vaccination is a critical component of an equine health maintenance program. Veterinarians play a crucial role in client education, risk assessment, and herd evaluation to determine which vaccination program is best suited for an individual horse or herd. Selection of vaccinations must take into account the horse's age, sex, geographic location, use of the horse, pregnancy status, risk for developing disease, and associated costs of immunization to the client. The anticipated effectiveness of the selected products should also be considered. The AAEP amended their guidelines for vaccination of the horse in 2008, with updated information in charts on their website www.aaep.org. The relevant updated information will be presented here, as well as a review of some of the current literature on the available USDA licensed products for vaccination. As a general rule, all adult horses need to be boosted at least annually. Pregnant mares should receive booster vaccinations 4 to 6 weeks prior to expected foaling, and vaccination for EHV-1 at 5, 7 and 9 months of gestation. Modified live vaccinations are typically avoided in pregnant mares. Foals typically should begin immunization series from 4-6 months of age, unless the mare was not vaccinated (begin at about 3 months of age). Maternal antibody interference may occur in young foals that received adequate colostral antibodies, and results in a decreased immune response to vaccination. Foals with residual maternal antibodies typically produce a greater serologic response to vaccination when an initial series of three doses is administered rather than the typical 2 doses.

Core vaccinations

Core vaccination has been defined by the AVMA as "those that protect from diseases that are endemic to a region, those with potential public heath significance, required by law, virulent/highly infectious, and/or those posing a risk of severe disease. Core vaccines have clearly demonstrated efficacy and safety, and thus exhibit a high enough level of patient benefit and low enough level of risk to justify their use in the majority of patients." The AAEP has identified tetanus, eastern and western equine encephalomyelitis, West Nile virus, and rabies as core vaccinations for every horse. These vaccines are recommended irrespective of age, use, or geographic location. Frequency of EEE/WEE vaccination may differ based on geographic region.

Tetanus

All horses should be vaccinated annually for tetanus. Previously unvaccinated horses should receive the initial series of 2 doses given 3-6 weeks apart. Foals require an initial 3 dose series beginning at 4-6 months of age if the mare was vaccinated. The currently available products are formalin-inactivated, adjuvanted toxoids; and are considered both safe and effective if given per manufacturer recommendations. Intervet, Pfizer, and Boehringer Ingelheim (BI) make tetanus toxoid singly, and in combinations with eastern/western/venenzuelan encephalitis and influenza. The tetanus toxoid antigen induces strong serologic responses and circulating antibody results in complete protection against tetanus. Holmes et al looked at immune responses to commercial equine vaccines against EHV-1, influenza, EEE, and tetanus. The study compared antibody responses to tetanus in 3 products: Intervet's EncevacT™, Fort Dodge's Equiloid™, and Boehringer's Cephalovac EWT™. All of the vaccines produced titers significantly different from the control group. IgGb titers were higher in the horses vaccinated with EncevacT; however, all vaccines resulted in titers higher than the controls (Holmes et al, 2006). Challenge studies of the vaccinations have not been published.

Encephalomyelitis

Vaccination for EEE and WEE is recommended for all horses in or traveling to North America. Although WEE is most typically seen in the west and mid-western states, sporadic cases have also been recognized in the northeast and southeast. VEE is a reportable foreign animal disease, and has not been reported in the United States for over 20 years. VEE results in a higher level of viremia than EEE or WEE, which makes direct horse to horse or horse to human transmission possible. Vaccination of adult horses for EEE/WEE should be done annually in the spring prior to mosquito season. In endemic areas where mosquitoes are active year round, such as Florida, vaccination is recommended as often as every 3-4 months. Foals of vaccinated mares should begin a 3 dose series at 5-6 months old, while foals of unvaccinated mares should begin a 3 dose series at 3 months of age. Early intracranial challenge studies demonstrated 100% protection using the formalin inactivated EEE/WEE vaccinations. This author has seen a confirmed EEE case 7 months after vaccination in a 4 year old that was routinely vaccinated, so routine booster vaccination is critical. In the previously mentioned study by Holmes et al, Intervet and Fort Dodge's vaccinations generated higher specific antibody responses than BI's EEE vaccine. However, this is in contrast to the superior responses obtained using BI's respiratory viral vaccine. These results may be affected by the different adjuvant preparations utilized by the manufacturers, as the adjuvant preparation will effect the immune response to vaccination.

Vaccination against VEE remains controversial because it may confound diagnostic testing in an outbreak. The USDA recommends vaccination only when there is a serious threat that the disease may spread into the United States. The only available vaccines are killed products; however, in an outbreak, a conditionally available modified live vaccination has been previously released. Fortunately, Walton et al demonstrated that there may be cross-protective immunity in horses that are vaccinated for EEE/WEE to VEE. Vaccination against EEE showed the best cross-protective response, and protected all of the horses challenged with VEE. Vaccination with a combination of EEE/WEE will also result in cross-protection.

West nile virus

West Nile virus vaccination is recommended at least annually for all adult horses, with a 1-3 dose primary series for foals, depending on the product chosen. To this author's knowledge, the killed and recombinant vaccinations have not been labeled specifically in foals. Multiple vaccines are currently available for WNV immunization.

A study published in 2007 by Seino et al compared the efficacies of three available vaccines against intrathecal challenge with West Nile virus. All control horses (6) in the Seino study demonstrated moderate to severe signs of WNV post-challenge and resulted in 0% survivors. All vaccines resulted in 100% survivorship after severe challenge with WNV. None of the horses vaccinated with the chimera vaccination developed clinical signs of WNV; while 1/5 horses vaccinated with the recombinant canary pox vaccine developed mild signs of disease and 4/6 horses vaccinated with the killed vaccine developed mild to moderate signs of disease later in the study period. The authors noted that small numbers of horses used in this study may have influenced the outcome, as a previous study demonstrated 1/20 horses vaccinated with the chimera vaccine to develop mild clinical disease. All available vaccines are effective at 28 and 56 days post-infection. The chimera vaccination is labeled for 12 months against clinical disease. Since long-term immunity is not typically a feature of inactivated vaccines, vaccination with killed products bas been recommended more frequently (bi-annually) in endemic areas such as Florida.

Rabies

Rabies is recommended as a core vaccination in horses. The disease is endemic in the wildlife population in most of the eastern seaboard of the United States. Cases of rabies in horses and mules increased 12.8% from 2005 to 2006 according to Blanton et al's rabies surveillance publication. Intervet, Fort Dodge (Pfizer) and Merial all make killed vaccines licensed for use in the horse. EquiRab®, a rabies vaccine designed specifically for use in horses, was released in 2009 by Intervet. It is labeled for 14 months of protection and is safe for foals and adults 4 months of age and older. For foals, rabies immunization is a 3 dose series (3rd dose at 10-12 months old) beginning at 3 months (unvaccinated dam) or 6 months (vaccinated dam) of age. Correlation between rabies titer and protection is not known in the horse. However, titers are used to predict protection in vaccinated people. Challenge studies demonstrating efficacy are required for licensing of all rabies vaccines (including those used in horses). The studies must indicate a twelve month duration of immunity, and a minimum of 80% of vaccinated animals must be resistant to severe challenge with rabies virus.

Rabies vaccines are not licensed for use in pregnant mares; however, only a limited number of vaccines are licensed for use in the pregnant mare (herpesvirus, rotavirus, and strangles). Rabies vaccines are frequently given to pregnant mares, but may also be boosted prior to breeding since antibody levels are maintained to provide adequate passive transfer. Vaccinated horses that are exposed to a confirmed rabid animal should be immediately revaccinated and observed for 45 days for clinical signs. Unvaccinated horses exposed to a confirmed rabid animal may be euthanized or isolated under close observation for 6 months. Consultation with the state veterinarian is recommended for unvaccinated horses, as the Texas post-exposure prophylaxis protocol (immediate vaccination for unvaccinated exposed animals) has demonstrated excellent efficacy against infection.

Recommendations for non-core vaccinations

Anthrax

Fortunately, anthrax occurs in only a limited geographic region of the country where alkaline soil conditions are favorable for the organism's survival. Anthrax is more commonly reported in central or south America, but has been identified in Texas, the Dakotas, Minnesota, Florida, and others. Anthrax is a rapidly fatal septicemic disease caused by proliferation and spread of Bacillus anthracis. Vaccination is indicated for horses pastured in endemic areas. The available vaccination is a live strain and not recommended for use in pregnant mares. Additionally, concurrent use of antibiotics is not recommended as it may interfere with the immune response to vaccination. The vaccine is administered subcutaneously, and requires a primary series of 2 doses followed by annual revaccination. Age specific guidelines for vaccination of foals are not available for this vaccination. Care should be taken during handling and storage of this product to prevent accidental human exposure.

Botulism

Clostridium botulinum produces 8 toxins that can block transmission of nerve impulses, resulting in the weakness and paralysis that are observed from clinical disease due to botulism. Toxin types B and C are associated with the most outbreaks of botulism in horses, and only a vaccine for C. botulinum type B is licensed for use in the horse (BotVax B®, Neogen). A recombinant vaccination for neurotoxin C has been evaluated in a European study by Frey et al and showed fewer injection site reactions and induced similar concentrations of neutralizing antibody to the available vaccine, but is currently not available in the United States. The primary indication for vaccination is for the prevention of Shaker Foal Syndrome (toxicoinfectious botulism) which is the result of toxin produced by vegetation of ingested spores within the gastrointestinal tract. Shaker Foals are most common in Kentucky and the mid-Atlantic states. Vaccination is recommended at 4-6 weeks pre-partum for previously vaccinated mares. Unvaccinated pregnant mares in endemic regions can be vaccinated with the primary series during pregnancy at 8, 9, and 10 months of gestation. Foals of vaccinated mares can begin the three dose series at 3 months of age, after maternal antibodies begin to decline. Foals of unvaccinated mares may benefit from plasma transfusion from a vaccinated horse or administration of botulism antitoxin. One study suggests that foals vaccinated at 2, 4, and 8 weeks of age will develop an adequate serologic response even in the presence of passive maternal antibodies, but further study needs to be done.

Equine herpesvirus (EHV-1 and EHV-4) also known as Rhinopneumonitis

Equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4) typically infect the respiratory tract in the first few weeks to months of the foal's life. Clinically apparent infections are usually seen beginning in weanlings up through older horses in training, especially in horses that are commingled. Clinical signs of EHV-1 may include respiratory disease, abortion, neonatal death, or neurologic disease. EHV-4 most commonly causes respiratory disease, however it has caused neurologic disease in isolated cases. There are currently no vaccines labeled to prevent neurologic disease attributable to EHV. Although most mature horses develop some immunity to the respiratory disease caused by EHV through repeated exposure, horses are not protected against the abortigenic or neurologic forms of the disease. Mature horses are actually more commonly affected by the neurologic form of the disease compared to younger animals.

Vaccination is recommended to prevent abortion in broodmares, and to reduce the signs and spread of respiratory disease in foals, weanlings, yearlings, and performance horses that are at high risk for exposure. Vaccination may reduce viremia and days of viral shedding. Multiple killed vaccines and one modified live vaccine (Rhinomune®) are available for protection against EHV-1. The vaccines licensed for respiratory disease contain a lower antigen load than the vaccines labeled for both respiratory disease and abortion. The killed high antigen load vaccines (labeled for abortion) typically result in higher antibody responses and some evidence of cellular response to vaccination. Subsequently, AAEP recommends choosing the high antigen load vaccines over the low antigen load vaccines for immunization when cost is not a factor.

In pregnant mares, vaccination with a killed product labeled for abortion is recommended at 5, 7, and 9 months of gestation. Some veterinarians advocate an additional dose at breeding and at 3 months of gestation. This is likely due to the findings in the study by Holmes et al, which looked at serology and measured EHV-1-specific interferon-gamma in response to vaccination with Prodigy™ and Pneumabort K™. Both vaccines generated significant antibody responses and show evidence of EHV-1 specific interferon production. However, interferon responses were only observed after the third dose of vaccination, so protective cellular responses may not be occur until near the end of gestation if immunization is begun at 5 months of pregnancy. Stallions and barren mares on breeding farms should also be vaccinated prior to breeding season and thereafter based on the risk of exposure. Foals should be vaccinated with the first dose of killed of MLV vaccine starting at 6 months of age, a second dose one month later, and a third dose 3-6 months after that. Booster vaccination is recommended at 6 month intervals. All horses less than 4 years of age should generally be vaccinated. Booster vaccination should be continued every 6 months for horses on breeding farms (or in contact with pregnant mares) or performance horses with higher risk of exposure.

Equine viral arteritis

Equine arteritis virus can cause abortion, vasculitis, pneumonitis and death in newborn foals, and occasionally establish a long term carrier state in infected stallions. Most horses become infected via inhalation and invasion of the respiratory epithelium. Fortunately, most infected horses make good recoveries and mortality is uncommon. This disease can have a significant economic impact on breeding populations and venereal spread by infected stallions is the predominant route of spread. Because clinical signs can mimic other viral infections, laboratory confirmation is required for diagnosis. Antibody titers cannot differentiate natural infection from vaccination, therefore, testing prior to vaccination is recommended for all first time vaccinates. Vaccination is available with ARVAC® (Pfizer), a modified live vaccine. The vaccine is considered safe for all horses with the exception of pregnant mares in their last 2 months of gestation or foals less than 6 weeks of age. Vaccination is not effective at eliminating the carrier status of infected stallions. However, it should be noted that spontaneous clearance of the carrier state may occur in infected stallions months to years after initial infection. (Timoney ACVIM 2008) Vaccination in the face of an outbreak has been effective at controlling the dissemination of infection within 7-10 days.

The indications for EVA vaccination are to protect stallions against infection and the development of a carrier state, to immunize negative mares before being bred with EAV-infective semen, and to curtail outbreaks of the disease. Consultation with the state veterinarian is recommended prior to implementing a program to ensure compliance with the state's control program, if there is one. Additionally, some countries will not allow import of seropositive horses, regardless of vaccination status. These requirements should be taken into consideration prior to the development of a vaccination program. Stallions being vaccinated for the first time should be isolated for 4 weeks prior to breeding. Colts should be tested and begin vaccination at 6-12 months of age. Annual vaccination should be performed after that. Vaccinated mares should be isolated from seronegative horses for 3 weeks to allow time to develop immunity prior to breeding and to decrease the incidence of post-vaccination shedding of the virus. First time vaccinates shed virus in their nasopharyngeal secretions in 40-60% of cases for generally less than 1 week (Timoney, ACVIM 2008). Seropositive mares do not require vaccination prior to being bred to a positive stallion; however, they should be isolated for 24 hours after breeding to avoid transmission of virus through voided semen.

Influenza

Equine influenza A type 2 is endemic in the equine population in the United States and throughout much of the world. As a general rule, almost all horses should be vaccinated against influenza unless they live in a closed and isolated facility. Mature performance, show or pleasure horses should be revaccinated at 6 month intervals. According to the AAEP, all currently marketed equine influenza vaccines, including the MLV as well as the inactivated products, are likely to provide protection of at least 6 months duration. The performance of the current vaccines in the future will depend on the inclusion of any new antigenically distinct influenza viruses that may occur.

The three types of vaccines currently available are killed vaccines, modified-live cold-adapted equine influenza/A2 vaccine (intranasal), and the canary pox vectored vaccine. The killed influenza vaccines have been shown to be effective in providing protection against clinical disease and viral shedding. A three dose initial series is recommended. The intranasal vaccination is safe and effective as a single immunization to naïve horses. Circulating antibody responses following the intranasal vaccination are minimal; therefore, it is not recommended for mares in late pregnancy to boost colostral antibodies. Local protection at the nasal mucosa is likely enhanced with this vaccination. Although it is labeled for vaccination in horses >11 months old, it does appear safe and effective when administered to foals six months and older. The canary pox vector vaccine (Merial) is administered IM and provides at least 6 months of protection. The vaccine is considered safe in foals as young as four months of age. The study done by Minke et al examined the efficacy of the canary pox vaccine against challenge with influenza virus and demonstrated clinical signs and viral shedding to be significantly reduced in vaccinated horses.

Vaccination to boost immunity in the face of an outbreak may be beneficial if the outbreak is detected early enough. In previously vaccinated horses, any vaccine product may boost immunity in an outbreak. In unvaccinated horses, the early onset of immunity (7 days) after administration of the intranasal vaccine may make it more beneficial for use in that situation.

Potomac horse fever

Infection with Neorickettsia risticii can cause colitis, colic, laminitis, and abortion in pregnant mares with fetal infection. The currently available commercial vaccinations are inactivated, adjuvanted products. The vaccines are not labeled for prevention of abortion. Field evidence of the benefit of this vaccination is lacking, and the effectiveness of the vaccination has been questioned due to lack of seroconversion (Dutta et al 1998). Additionally, only one strain of the organism is present in the available vaccines, while multiple field strains have been identified. If vaccination is elected in at risk populations of horses, it is recommended in spring prior to peak incidence in the summer and fall. The primary series is two doses administered 3-4 weeks apart. The manufacturers recommend vaccination at 6-12 month intervals. Vaccination of foals is recommended at or after 5 months of age if the mare has been vaccinated.

Rotavirus

Rotavirus can be a significant cause of foal diarrhea and morbidity on breeding farms. The available vaccination is an inactivated rotavirus Group A (Pfizer) and is indicated for use in pregnant mares to increase concentrations of colostral immunoglobulins against rotavirus. In the field study done by Powell et al, the incidence of rotaviral diarrhea was lower in foals born to vaccinated mares, compared with foals born to control mares, but the difference was not significant. Vaccination is considered to be safe. Additionally, there is no data suggesting that vaccination of newborn foals is effective. Vaccination of pregnant mares is recommended at 8, 9, and 10 months of gestation.

Strangles

Vaccination is one method for prevention and control of infection with S. equi. Vaccination is recommended on farms where S equi has been an endemic problem or for horses expected to be at a high risk of exposure. With strangles, vaccination will likely reduce the severity of disease in the majority of horses that are infected, but will not result in complete disease prevention. Available vaccines can be administered by intramuscular (Intervet, Boehringer Ingelheim) and intranasal routes (Pfizer). Improper administration of the vaccination can result in poor protection against infection and/or complications at the site of injection. The inactivated vaccines have reduced the severity of clinical signs and reduced the incidence of disease by as much as 50% during outbreaks. The injectable vaccines are associated with increased injection site reactions when compared to other equine immunizations. The intranasal vaccination has stimulated high levels of immunity against experimental infection, and will result in excellent local immunity if properly administered. Slowly developing mandibular abscesses have occurred in a very small percent of cases due to residual vaccinal organism in the modified live product.

Vaccination is generally not recommended during an outbreak of strangles. If there are horses on the farm with no clinical signs of infection and no known contact with sick horses, vaccination may be considered. Horses that have had the disease within the previous year also do not need to be vaccinated. Once recovered from an active infection, 75% of horses have immunity for 1-5 years. It is generally recommended that recovered horses have titers checked prior to additional vaccination. Vaccination of horses recently exposed to strangles (that have high antibody levels) may result in purpura hemorrhagica. Vaccination is generally only recommended in healthy horses with no fever or nasal discharge. Manufacturer recommendations may vary slightly; however, vaccination with inactivated products may have improved efficacy if a primary series of 3 doses of vaccine followed by booster doses at 6 month intervals. Vaccination with the modified live intranasal product requires a 2 dose series and annual or semi-annual booster for adults. The modified live vaccine has been administered in foals as young as 6 weeks of age, but its efficacy has not been evaluated. It is generally recommended to start the intranasal vaccination in foals 6 to 9 months of age with a 2 dose series. The ACVIM consensus statement on equine strangles can provide additional information on diagnosis, treatment, and management of this disease (Sweeney et al 2005).

References

http://www.aaep.org/vaccination_guidelines.htm

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