Investigating Horse Immunity

The latest equine immune system research in horses young and old.

The immune system is an amazing concept in both man and beast. It allows us to survive in a very complex world filled with harmful bacteria and viruses that can use our bodies for nourishment and reproduce within us. The immune system protects us from those organisms both by limiting their entrance into our bodies and helping rapidly eliminate the ones that manage to make it past those initial defenses (e.g., the skin, hairs within the nasal passages). Just as in humans, if a horse's immune system isn't functioning properly, he doesn't have a good prognosis for a long or healthy life.

There are several components to a horse's immune system. The structures or molecules that induce an immune reaction are called antigens, and these indicate to the immune system that a foreign and potentially dangerous material (such as a pathogenic [disease-causing] bacteria or virus) is present. The immune system then produces antibodies (special infection-fighting proteins) to destroy the invading organism. (Read a more detailed rundown of how the horse's immune system functions on page 23.)

Welfare and Research

Researchers throughout the world are studying the equine immune system and particularly, how it interacts with infectious diseases such as equine herpesvirus, influenza, and Streptococcus equi (the bacterium that causes strangles). D. Paul Lunn, BVSc, MS, PhD, MRCVS, Dipl. ACVIM, professor and head of the department of clinical sciences at Colorado State University's (CSU's) James L. Voss Veterinary Teaching Hospital, is part of a group studying equine influenza virus and equine herpesvirus-1 (EHV-1). This research team is evaluating how some of the current vaccines against these diseases trigger the immune system to produce antibodies that protect horses from developing disease. But, most importantly, this group is working to develop new models for studying these infections. According to Lunn, these models could improve equine welfare in a research setting by allowing scientists to complete their work in vitro (in the laboratory, not in the live animal), thereby enabling them to develop new drugs and vaccines in a more ethical, efficient manner.

"Dr. Gabi Landolt, PhD, Dipl. ACVIM, and Dr. Gisela Soboll, PhD, (both faculty members at CSU) created a model where we can grow an artificial equine respiratory tract lining," says Lunn. "We have this in an incubator, and now we can study how influenza virus and EHV-1 interact with it. This is important because (the virus') first interaction with the surface of the respiratory tract has an enormous effect on the disease outcome. With the artificial lining we can do a lot of studies we could never do or would want to do in a living horse."

Another CSU researcher, Lutz Goehring, MSc, Dipl. ACVIM, PhD, assistant professor in equine medicine, has developed some of the most original models of the blood system of the horse's brain and spinal cord. Currently, Goehring is studying how EHV-1 causes neurologic disease.

"That's an enormous problem in the equine industry," adds Lunn. EHV-1 is highly contagious and responsible for significant economic losses due to respiratory illness, abortion, neurologic (paralytic) disease, and death in horses. "Because of this new system he is making some groundbreaking discoveries. These new technologies enable us to determine what (drugs and vaccines) will work and what will not without having to cause diseases in the horse. We are constantly trying to reduce our impact on the (research) animals while at the same time making discoveries that are helpful," he says.

New Research in Neonates

Foals are born with competent immune systems, but these systems still require maturation to be maximally effective. David W. Horohov, PhD, the William Robert Mills Chair in Equine Immunology at the University of Kentucky's Maxwell H. Gluck Equine Research Center, says researchers are studying a dam's role in the development of her foal's immune system. How the mare is fed, housed, and exercised, plus the amount of stress she's under, could impact her foal's immune system both early on and later in life.

"We used to think a healthy foal was enough," says Horohov. "But in reality there may be other issues not yet apparent. We're not just talking about the genes that the mare passes on or the antibodies in her colostrum (first milk), but also how the maternal environment influenced the development of the animal's immune system. We're beginning to have a better appreciation for the epigenetic (nongenetic) effects that the mom has on the DNA of the foal and its ability to respond to the environment from an immunological standpoint."

Horohov's research group is also studying mares' colostrum to determine how maternal vaccination impacts the immune system response of the foal that has consumed that colostrum. "We know vaccinating the mare is important to develop proper colostral antibodies (also known as maternal antibodies)," he says. "But we are asking what else does that do and how does it help the foal respond to vaccine?"

Thus far Horohov and his colleagues have observed that maternal antibodies can block the foal's response to multiple types of equine influenza vaccines. This might be in part a mechanism to allow the foal to "tolerate" the maternal antibodies themselves, as they also are foreign proteins. While it makes pinpointing timing of foals' first vaccinations a challenge, the protective antibodies from colostrum are absolutely vital for foals. For example, notes Lunn, in North America where exposure and vaccination to influenza virus is common, leading to flu-specific antibodies in colostrum, veterinarians rarely see influenza in foals causing significant disease. However, during the 2007 Australian outbreak many foals died due to their lack of this maternal antibody. Thus, he says, owners still need to follow a veterinarian-recommended vaccination schedule for mares to prevent influenza infection in foals and weanlings. (More information on building immunity in foals)

New Research in Seniors

As a horse ages he develop immunosenescence, a decrease in his body's ability to respond to immune challenges. Previous studies have shown that the horse's immune response to vaccines decreases with age; however, it's unknown whether this means aging impacts vaccine efficacy.

Basically, vaccines can be comprised of a killed virus or a live virus that has been modified in a laboratory so it no longer causes the disease. Both vaccine types can elicit an immune response, but depending on the disease or the individual, one type might be preferable over the other.

"We just had a paper come out on this topic," says Horohov. "It shows that senior horses respond quite well to live virus-vaccine--in this case it was a canarypox (-vectored) vaccine for influenza. Previously, studies had shown that old horses tend not to respond to traditional killed (influenza) vaccines. So it was exciting to try this new product and have success." While Horohov's study reveals that aged horses can respond to this particular vaccine, he notes that his team has not tested other vaccines in a similar manner to determine which is most effective in this population--live or killed.

Additionally, the team made observations in an unvaccinated group that are useful for owners managing older horses. These animals, which had an extended history of being vaccinated for the virus prior to the study, were not vaccinated against influenza for two years prior to researchers challenging them with the virus. These unvaccinated senior horses were susceptible to influenza, and all of them became ill. Although older horses are generally less susceptible to equine influenza than their younger counterparts, Horohov says these study results drive home the point that older horses still need to be vaccinated against the disease if they are at risk for exposure.

Research in Performance Horses

Another ongoing study at the Gluck Center involves exercise's effects on the immune system. Horses exhibit chemical and immunological markers of inflammation (a response of tissues to irritation or injury that serves as a protective mechanism) immediately and even for several hours post-exercise. Researchers are questioning whether this is a good or bad process.

"We tend to look at the immune system as a protection against infectious disease," says Horohov. "But the immune system also expresses inflammation. Inflammation is sometimes a good thing, for instance in wound healing where it marshals the forces needed to get rid of infection. Problems occur when inflammation persists--then it becomes damaging."

During the past year Gluck researchers have been studying a group of Thoroughbreds in training, noting the production of inflammatory markers as the horses go through their training periods and the effects of various treatments for inflammation after exercise. "In human medicine it's thought that inflammation is part of the exercise response and probably plays a role in some of the muscle building and repair that occurs as a result of the trauma of exercising, either through lactic acid accumulation or physical (microtearing) of the muscle cells," says Horohov. "Chronic inflammation is bad but acute inflammation is probably necessary (for muscle repair)."

And similar to what humans experience, as the horse's body adjusts to training, less stiffness and soreness occurs. "So we think that the immune system is undergoing a conditioning effect as well," says Horohov. "Our hypothesis is horses that train successfully will have decreased inflammatory markers post-exercise. And those who are at risk for injury will have elevated levels of inflammatory markers throughout the training period."

Although this study is still under way, Horohov says evidence suggests that the use of non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation might also impair the immune system's ability to adapt to training. "There was a report (from Gluck) by Dr. Tom Tobin (DVM, PhD, Dipl. ABT) a couple of years ago where he looked at racehorses who suffered significant injuries and found that they all had received NSAIDs in the past," he says. "Pain is a signal that something is wrong, and when you give animals something that masks that pain perhaps the injury is only going to become greater."

Horohov and his colleagues will also be studying nutritional supplements that manufacturers say reduce inflammation, in order to determine the supplements' effects on long-term health and training-related injuries.

Research in Nutrition

People have long recognized that vitamins and other compounds can yield health benefits that extend to immunological function. For instance, the immune system can lose some functionality when faced with the overproduction of oxygen radicals (also called free radicals--a product of the inflammatory processes--these chemical forms of the oxygen molecule are highly reactive and capable of causing damage to cell membranes, proteins, and DNA). Adding antioxidants such as vitamins C and E and omega-3 fatty acids to the diet can reduce the amount of inflammation and oxidation that occurs and, therefore, the immune system can respond in a more specific matter.

"If your horse is otherwise healthy, is eating properly, and is not under any physical or psychological stress then he's probably doing fine," says Horohov about when to supplement with the immune system in mind. "On the other hand, who is not under stress? So by using these materials in a preventative manner you're helping to enhance overall competency of the immune system."

Horohov cautions that it's impossible to super-charge the immune system--all you're really doing is "topping off the tank." If your horse already has a healthy immune system then supplements aren't going to improve it. "Where we get into concern is when people start to make claims beyond that, especially if there haven't been enough studies to support the claims," says Horohov. "Not to say there aren't benefits in the supplement, but one has to be a little bit cautious." Each horse's situation is unique--he could be stressed, older, in heavier work, or a combination of these. Consult your veterinarian, nutritionist, or extension specialist before adding supplements labeled as immune boosters to your horse's diet.

Take-Home Message

Vaccination recommendations have changed over the years based on researchers' growing understanding of the horse's immune system and how it works. In fact, Horohov notes that many veterinarians and horse owners used to be concerned about potential resistance of viruses/bacteria to vaccines, but that this was when vaccines were overused. Currently, veterinarians encourage owners to employ a strategic plan that includes core vaccinations for all ages (see page 26) and risk-based vaccines per horse and situation.

Lunn says that, along with vaccination, it's also important to employ biosecurity measures such as quarantining new horses to protect the animals in your stable.

Consult your veterinarian on how to do this, and have him or her review your farm or barn to give you some hints on simple biosecurity principles you can follow. There are also steps you can take in your horse's daily care to protect his immune system. "Good nutrition is the best immune stimulant there is," says Lunn. "Make sure your horse has a well-balanced diet so he has all the micronutrients--minerals and vitamins--he needs. The immune system is pretty smart in the horse, and for most of their lives this is all the help they need."

About the Author

Sharon Biggs Waller

Sharon Biggs Waller is a freelance writer for equine ­science and human interest publications. Her work has appeared in several publications and on several websites, and she is a classical dressage instructor.

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