Navigate the complex world of vaccine types, mutations, and efficacy

At the threshold of the paddock I paused, in awe of what I was witnessing. A beautiful dun Morgan mare lay flat on the ground, her devoted owners hovering over her, holding an umbrella to shield her from the baking sun. The mare would try to sit sternal with great effort. With a lumbering heave, she’d hoist herself up on her front legs just enough that her owners could help her flip to the other side. Her limp hind legs were useless, completely paralyzed. Despite not understanding what was happening to her, she had enough survival instinct to try to roll over to relieve weight on her lungs and huge haunch muscles.

I’d seen horses with similar clinical signs— hallmarks of West Nile virus (WNV) encephalitis, which had recently emerged and spread across the United States. Subsequent blood tests confirmed WNV infection.

While this mare did not have the advantage of a vaccine to keep her safe, today we have at least four vaccines licensed to protect horses against WNV, along with many others to guard against the variety of diseases they face. Let’s look at the science behind the routine use of immunizations for our horses.

Why Are Vaccine Programs Important?

David Horohov, PhD, director of the Maxwell H. Gluck Equine Research Center at the University of Kentucky, in Lexington, is renowned for his work with equine immunity against a variety of pathogens (disease-causing organisms).

“Infectious diseases remain a major cause of concern in both human and veterinary medicine,” he says. “As the current COVID-19 pandemic so dramatically demonstrates, the introduction of an infectious agent into a susceptible population can have devastating consequences. The purpose of a vaccine is to stimulate a protective immune response that either prevents infection or limits seriousness of disease.”

Horses are susceptible to a number of viral and bacterial diseases for which the equine industry has produced safe and effective vaccinations.

“Vaccines really come into their own if enough individuals in a population are vaccinated to achieve herd immunity,” says Janet Daly, BSc, PhD, FHEA, FRCPath, professor of viral zoonoses at the University of Nottingham School of Veterinary Medicine and Science, in the U.K.

Herd immunity is the theory that when a high proportion of individuals in a population develops immunity against an infectious disease after previous infection or vaccination, the spread of that disease slows. So, the more horses you vaccinate within a herd, the fewer cases you’ll see in unimmunized animals. Herd immunity occurs when the number of immunized individuals exceeds 75% and preferably ranges from 83-94%, says Daly.

“In these circumstances, outbreaks can be prevented and so everyone benefits, including individuals that respond poorly to vaccination,” she adds.

In equine medicine, veterinarians recommend administering core vaccines annually to every horse. These include immunizations against Eastern and Western equine encephalomyelitis, tetanus, WNV, and rabies. Horses might also require risk-based vaccines such as those against influenza, leptospirosis, rhinopneumonitis, strangles, botulism, and Potomac horse fever. Whether a veterinarian recommends a risk-based vaccine for a horse depends on the animal’s likelihood of being exposed to the particular disease, as determined by geography, travel, season, and congregation with other horses. Daly points out that some diseases we vaccinate against, such as influenza, are rarely fatal, yet some individuals can develop serious complications from infection.

Types of Vaccines

Vaccines come in several forms, the most common of which are inactivated (killed) or modified live (attenuated). Inactivated vaccines contain relevant components of a disease agent, but they are treated with heat or chemicals to quell their pathogenicity, or disease-producing capacity. Killed pathogen vaccines are fairly easy to manufacture, relatively inexpensive, and won’t cause disease, says Daly. A killed vaccine presents the horse with the inactive proteins (antigens) necessary to generate an antibody response.

The viruses or bacteria in modified live virus vaccines are capable of reproducing in the horse, but their pathogenicity has been reduced and isn’t likely to cause disease. These vaccines stimulate a more pronounced and longer-lasting response to immunization than killed vaccines.

“Although uncommon, there is a risk with some live attenuated vaccines that they could ‘revert’ to virulence to cause disease, particularly in an immune-compromised individual,” says Daly.

The main advantage of using “live” antigens, says Horohov, is that the vaccine better imitates the natural immune-stimulating process to generate an optimal protective immune response. “This is particularly important when a naive (not previously exposed) individual is vaccinated for the first time,” he says. “It is less important for horses with either prior exposure to the disease, or their history includes routine vaccination against that disease. However, we have relatively few live-agent vaccines available for horses.” The most common modified live vaccines are the intranasal equine influenza vaccine and the intranasal strangles vaccine.

Manufacturers also use recombinant technology to produce some equine vaccines. On its website the American Association of Equine Practitioners explains how these are engineered in various ways:

1. Live attenuated vector vaccines incorporate pathogenic antigens into a harmless virus or bacteria;
2. Chimeric vaccines substitute genes from a pathogen for similar genes in a safe but closely related organism; and
3. DNA vaccines consist of a DNA plasmid (a small DNA molecule found in bacteria and other cells) that encodes a viral gene that is then expressed in the horse following immunization.

When a vaccine contains more than one kind of antigen—such as the five-way Eastern and Western encephalomyelitis, tetanus, influenza, and rhinopneumonitis vaccine many veterinarians give in the spring—it’s referred to as a combination vaccine. Horohov and Daly agree that combination vaccines offer convenience and cost savings compared to separating each disease antigen into individual vaccines, given one at a time with multiple sticks and/or veterinary visits. Both list occasions when a single-antigen vaccine might be necessary: when a horse has a history of an adverse reaction to a combination vaccine, for example, or when it is necessary to vaccinate against a specific pathogen due to exposure in an outbreak, such as with equine influenza. Vets also commonly administer vaccines containing just one or a limited number of antigens (e.g., rhino/flu, rabies, Potomac horse fever) to provide comprehensive protection while keeping the horse’s welfare in mind.

Viral Mutation

Certain diseases develop strategies to evade detection by the immune system, such as through “plasticity” of their genomes, says Horohov. “This is best exemplified by influenza viruses, which use RNA as part of their genome compared to DNA molecules of mammals. Replication of RNA (which is how viruses proliferate once they’ve infected host cells) is much more error-prone compared to DNA(that tends to correct error), leading to a greater likelihood for mistakes or mutations to occur during viral replication.”

“High rates of replication in RNA viruses are like writing out text from a book lots of times very rapidly without the opportunity to correct any mistakes,” Daly explains. “Lots of subtly different virus particles are made during infection of one individual. Over time, the virus (variants circulating in exposed populations) may develop subtle outward differences from virus strains used in vaccines in a process called ‘antigenic drift.’ This eventually means that antibodies raised against the vaccine virus or from a previous infection no longer recognize and neutralize the virus that is circulating in the field.”

Changes in the RNA sequence that alter the virus’ structure might allow it to escape the host’s immune response, adds Horohov. Such mutations are passed on to replicating virus generations and lead to the emergence of new circulating virus strains. When this happens manufacturers must reformulate the target vaccines to include that ‘new’ mutated protein to elicit a host response.

“Fortunately, the equine influenza virus evolves more slowly than human influenza so equine vaccine strains do not need to be updated quite as frequently,” says Daly.

While human influenza vaccines are updated annually, equine influenza vaccines are only updated when the World Organisation for Animal Health (OIE) publishes new recommendations, which occurs infrequently, says Horohov.

Vaccine Frequency

You might be aware that your small animals only need to be immunized against certain diseases every three years. “Sufficient evidence has been accumulated for routine vaccination with core vaccines in dogs and cats,” says Daly (which, aside from rabies, are a different set of diseases). While immunizing small animals every three years against certain pathogens appears to provide adequate protection, other agents require annual administration.

“Most (small animal) vaccines have been through extensive trials of monitoring antibody levels over time to determine the interval at which revaccination is required based on how rapidly antibody levels decline and/or how well animals are protected when challenged with the pathogen at different intervals after vaccination,” she continues. “Studies such as these are difficult and costly to perform in horses.”

While corresponding duration of immunity (DOI) data are not available for most equine vaccines, Horohov says that generally the level of antigen-specific antibodies in a horse’s circulation, measured in blood serum as a titer to the agent of interest, tends to decrease fairly rapidly post-vaccination.

“Depending upon the magnitude of the initial antibody response to the vaccine, disappearance of detectable antibodies from the circulation may occur within a year’s time, if not sooner,” he says. “While antibody titers themselves are not always predictive of protection, it is assumed that disappearance of circulating antibodies is a likely sign of increased susceptibility to infection, and this dictates the need to revaccinate or booster frequently, according to manufacturer directions.”

During the initial licensing of a vaccine, manufacturers base their prescribed dosing method and frequency on experimental data they’ve obtained in studies using historical methods to induce immunity and assess protection.

“Typically, this involves administration of an initial priming dose, followed two to four weeks later by a second dose (a booster) of the same vaccine,” Horohov says. “This may be repeated based on other data that show when maximal antibody responses are obtained and a vaccine’s ability to stimulate an antibody response. A few weeks after the last vaccine dose is administered, challenge studies—exposure of the horse to the disease agent—are performed at the time when the expected maximal antibody response occurs. While it would be ideal that antibody titers would correlate with protection—something owners do ask about—this is not always the case.”

Titers Are Not the Answer

The major limitation in using titers to determine if a horse needs immunization has to do with protective immunity’s complex nature, says Horohov. He explains that the immune system responds to antigens in two ways—by producing antibodies (humoral immunity) and attacking antigens that have breached the cells (cellular immunity). When protective immunity involves cellular immunity, antibody titers provide little useful information.

Another reason titers aren’t helpful for measuring protection against diseases has to do with where the immune response must happen in the body to be protective, Horohov adds. A horse is best protected against a respiratory virus such as influenza when the immunization response is localized within the respiratory tract, for instance, which he says is one reason why intranasal vaccines work well.

“While there is some association between antibody titers in the blood and those present in the respiratory tract, it does not correlate well in terms of protection,” he says. “For many infectious diseases, the nature of the protective immune response remains poorly described, making it impossible to define what correlates with protection.”

Vaccination Pros and Cons

“Vaccines have received a lot of bad press in recent years,” says Daly. “There is no such thing as a perfect vaccine, but they can make the difference between life and death. Overall, vaccination is far less costly and stressful than infection.

Sometimes a horse develops a reaction to a vaccine, such as heat and swelling at the site of vaccination—this is a sign that the body’s immune system has been provoked into action. Major adverse reactions are, thankfully, relatively uncommon.”

In some cases the adjuvant—a vaccine ingredient used to modulate or amplify the immune response—is the culprit that evokes an adverse vaccine reaction. Sometimes, modifying the product or trying a different manufacturer’s vaccine can help mitigate such reactions.

“We have become complacent about what can be achieved by vaccination,” says Daly. “For example, many people today are unaware of the devastating impact childhood diseases had before routine immunization became available. Unfortunately, vaccine-preventable diseases are on the increase due to vaccine hesitancy in both human and pet populations.”

Take-Home Message

You probably wondered what happened to the mare in the introduction. She received every medication option and veterinary medical support, with the owners giving round-the-clock care to roll her every couple of hours and provide her with food, water, bedding, and shade. Her paralysis lasted four days. The morning they planned to have her humanely euthanized, 96 hours into her crisis, she stood up, shook herself, and miraculously recovered thanks to a robust immune system. She is one of the lucky ones; typically 40% of horses with WNV don’t survive.

A few remaining neurologic deficits persisted until the end of her life a decade later, but nothing that precluded her from being ridden. It is a desperate story with a happy ending, but how much better of a story had she been immunized and not contracted this disease in the first place.

As guardians of your horses, it helps to take advantage of every medical advancement that provides them with quality of life and longevity. Equine vaccines are protective in most cases, with very little downside to their use.

Horohov draws parallels between the immune system and the musculoskeletal system: “By exercising our horses regularly and building up strength in their muscles and bone, they can perform athletics at an optimal level. The same is true for the immune system. By ‘exercising’ the immune system through the routine use of vaccination, we allow our horses to optimally resist the infectious disease agents they may encounter.”