- Apr 1, 2000
Better vaccines, smarter protocols. These two areas are where efforts are being focused to provide improved and safer protection against infectious diseases. Experts, veterinarians, and horse owners are looking at a future where vaccines work better, where vaccines provide longer protection, and where vaccination programs are devised for the individual animal according to its circumstances and environment. In many cases, the future is here.
Recently, two new vaccines were introduced into the veterinarian's arsenal--Heska Flu Avert IN vaccine, which protects against equine influenza, and Fort Dodge's Pinnacle IN vaccine, which protects against strangles. Both promise to be more effective weapons than earlier vaccines for two reasons: They are administered intranasally and both utilize a modified live virus instead of a killed virus to stimulate a stronger immune response.
Intranasal vaccines work better than intramuscular vaccines in preventing respiratory infections, experts say, be-cause the nasal cavity or pharynx are where the bacteria or virus enters the respiratory system. Promoting an immune response where the virus first comes into contact with body surfaces--in this case, the mucous membranes lining the respiratory tract--produces more protection at the site. John F. Timoney, MRCVS, BSc, PhD, Keeneland Professor of Equine Infectious Disease, researcher (strangles vaccines), Gluck Equine Research Center, University of Kentucky, says that a mucosal response is very valuable in preventing infectious agents from getting into the respiratory system. "Very few if any injected vaccines are able to generate a mucosal response," he says. "The disadvantage of oral vaccines is they have to be packaged so they can travel through the stomach and the intestines. A lot of components are destroyed by the gastric acidity and digestive proteases, so the oral route is not so attractive."
Paul Lunn, MRCVS, BVSc, PhD, Dipl. ACVIM, associate professor, University of Wisconsin, has done a significant amount of research on equine immunology and resistance to infectious diseases. "Intramuscular injections do not produce enough immunity that will act in the respiratory system," Lunn says.
Modified live viruses increase and broaden (i.e., stimulate local, humoral, and cellular immunity) the immune response. Hugh G.G. Townsend, DVM, MSc, professor, Department of Veterinary Internal Medicine, University of Saskatchewan, has done research on vaccine efficacy. "Logically, modified live vaccines should produce more complete, longer-lasting immune responses than do killed vaccines," he says. "Their use should also result in us having to administer fewer doses of vaccine to both stimulate and maintain an effective immune response against disease."
"Use of modified vaccines is hardly an original idea," Lunn says. "The very first vaccine developed almost 200 years ago was a modified live vaccine. They are not used more commonly because of the potential for safety concerns and difficulty in their manufacture. They require more of the companies who produce them in terms of ensuring their safety. But frequently, modified live vaccines will work where killed vaccines may fail."
Previously, influenza and strangles vaccines did not offer reliable protection. "The strangles vaccine was probably the worst vaccine and the least efficacious product ever made," states Ronald D. Schultz, PhD, professor of veterinary pathology and Chairman of the Department of Pathobiological Sciences, school of veterinary medicine, University of Wisconsin. "Nor were the influenza vaccines very effective; they simply didn't work well."
In contrast, reports for Flu Avert and Pinnacle are encouraging. "Thus far, we have had some good reports with the new strangles vaccine," Schultz says. "But we've also had some instances where it's been used where there's been a complete break with strangles, so apparently it didn't provide protection." As regards the new flu vaccine, Lunn says, "I've worked with the new influenza vaccine, and I'm very impressed with the immune response."
Real Tests For Real Results
Shockingly, a major reason why many vaccines aren't as efficacious as desired might be because, in large part, manufacturers don't need to prove efficacy in order to obtain regulatory approval.
"The vast majority of the North American equine vaccines have not been examined for their efficacy in the horse," Townsend explains. "The basic challenge for the regulatory agencies is to make sure that vaccines are safe and pure. They do not, at this time, assure efficacy. For this and probably other reasons, less than a handful of the equine vaccines currently marketed in the United States and Canada have been critically examined for efficacy. There has been very little information published in peer-reviewed journals on the serologic response of horses to vaccination, protection against experimental challenge, or controlled field trials looking at vaccine efficacy in the face of natural disease. On the other hand, there are a number of reports of infectious disease, including respiratory disease, viral encephalomyelitis (sleeping sickness), tetanus, and rabies occurring in vaccinated animals."
In addition, when efficacy tests have been conducted, many were carried out in the laboratory and not in the field, a method that might not provide a true picture of how the vaccine will perform in animals. Robert E. Holland, DVM, a private practitioner based in Lexington, Ky., and a pharmaceutical consultant to several companies, says, "In the past, when serology showed there were antibodies present, we assumed that the vaccine was protective. Now we are finding out that might not always be the case." Consequently, Holland believes that vaccine manufacturers should test the performance of vaccines for non-fatal diseases in controlled challenge testing by administering the vaccine, challenging the vaccine by introducing the virus to the horse, and grading the vaccine accordingly.
Overall, equine vaccines really require a great deal of attention and improvement, says Schultz. "Quite frankly, the equine vaccine market isn't that big of a market, so if the money is not there, you're not going to see improvements made. In the past, there just hasn't been the impetus or the push to move in that direction."
Fortunately, Schultz and others believe that attitude is changing. Townsend agrees. "I think it would be fair to say that some vaccine experts--and probably many other people--are showing a greater interest in trying to insure greater effectiveness of equine vaccines."
Heska, for one, has apparently recognized that interest. Challenge testing was an important part of their Flu Avert studies and ranks as an important part of their marketing campaign; their Web site notes that Flu Avert is the "only vaccine proven in challenge studies to protect against equine flu" and "challenge studies are the industry's gold standard of evaluating a vaccine's ability to protect against equine flu."
Along the same lines of defining better measures of efficacy, researchers also are interested in exploring how long various vaccines are effective, how vaccines affect one another when used in combination, redefining the optimum time to begin foals on vaccines, and moving toward a vaccination program tailored to the individual horse.
Vaccinating youngsters in many species can be problematic. Too soon, and the antibodies received from its mother can inactivate the vaccine, leaving the youngster defenseless from the disease later on when maternal antibodies disappear. Too late, and the youngster is left unprotected for a time. Complicating matters, the age for which these maternal antibodies wane is not precise and varies to a degree from individual to individual. Veterinarians get around this by administering the vaccine followed by a booster a short time later.
This might be the case with equine influenza and herpesvirus 4. A study conducted by Holland and other researchers at the University of Kentucky found that the standard recommendation of vaccinating foals against flu at age two to three months is too early due to interference from maternal antibodies. "Now we recommend the foals be vaccinated at nine months, 10 months, and 11 months--three doses of inactivated killed influenza vaccine one month apart. In the case of Flu Avert, initial testing showed that one dose given at seven months followed by another dose at 11 months is effective in preventing horses challenged by the KY 98 influenza.
Similarly, researchers at the University of Kentucky found maternal antibody interference in young foals to equine herpesvirus 4. "We're asking those who work on equine herpesvirus to rethink foal vaccination strategy to try and prevent foals from getting the herpesvirus at about four to six months of age." Instead of beginning the herpesvirus vaccinations at age two months, Holland suggests waiting until the foal is four months old.
Starting vaccines too early, and thus giving them too often, might be the reason antibody levels aren't what they should be in the adult vaccinated horse:. "The maternal antibodies already present help suppress an antibody response to the vaccine," Holland says. "You can make them not respond as well because they have a level of antibodies already there protecting them. We're wondering, if you're vaccinating too young, could you be creating an effect that will be detrimental to the animal? We have no data to back that up, but we don't see the high titers (after vaccination) that we see when we waited until the maternal antibodies were gone (before starting influenza vaccination.)"
Combination vaccines also might contribute to reduced immune response. "In many instances, vaccines have been combined simply on a chronological basis," Schultz says. "The first vaccine was made, then the second added to the first, then the third added to those two, and so forth. There was no scientific basis whatsoever for adding them together. Furthermore, the potential influence of one over the other was not as well defined as it should be. We're now finding that in certain combinations, the addition of one component can really drive the immune response in the wrong direction, so you don't get the best protective immunity with the other component."
Others also question whether over-use of some vaccines--inefficacious products that require frequent boosters or very efficacious, annual vaccines that in truth offer protective immunity far beyond a year--can lead to secondary problems. Citing the equine herpesvirus (rhinopneumonitis) products, Schultz says, "Again, we have products that have low efficacy. When you have to use a herpesvirus product every two or three months in a pregnant animal to prevent potential adverse effects of the virus on the fetus, that's not good because vaccination of pregnant animals can be as dangerous as the virus itself. Nor is vaccinating Thoroughbreds at the racetrack every two or three months good for the animal.
"The stress of repeated vaccination alone," Schultz explains, "can have adverse effects on pregnancy and performance. Furthermore, the intimate association among the immune system, the endocrine system, and the nervous system could negatively affect certain horses that are vaccinated with single or multiple component vaccines on a two- or three-month basis. Developing products that provide at least a one-year duration of immunity should be a top priority to replace the less effective products that are currently used."
In the case of the tetanus vaccine, the duration of immunity in horses is unknown, even though vaccination is traditionally recommended every year. "In the human field, they used to give a tetanus vaccine every five years," notes Holland. "Now it's every seven years because they found the vaccine was protective for much longer than assumed. Now people are starting to re-evaluate tetanus vaccines in the horse."
Many feel that equine vaccines in general are not a health concern. "For the most part, the vaccines currently marketed are, in my view, remarkably safe," Lunn says. "The frequency of side effects from vaccination is rare in horses. Adjuvants (a substance included in inactivated vaccines to enhance the immune response) for the most part, do not cause severe reactions within the horse. Any vaccine you give needs to stimulate the immune response, and these have an affect on the animal, otherwise vaccination simply wouldn't work. With the advent of new commercial modified live vaccines, we will need to be particularly vigilant to ensure that we maintain our good safety record."
Lunn and others agree that owners should know about the diseases that threaten their horses and understand the risks of those diseases and the risks of the vaccines when deciding what to vaccinate against.
"In the past," he says, "we've taken the view that if an infectious disease is a threat, if it can possibly affect the horse, then we should vaccinate against it. That viewpoint probably is naive. It's more important to look at the vaccination in the context of just how serious the threat of the disease is, how common it is in a geographic area, and how common it is in a group of horses--i.e., groups defined by age or by performance such as competition horses, broodmare populations, backyard horses--then determine the pattern of disease in that population of horses."
The issue of over-vaccinating also includes throwing in extra vaccines just because they are part of an economical, six-for-the-price-of-one package.
"The point I'd like to get across is what you vaccinate with is a very important medical decision," Schultz emphasizes. "There shouldn't be this knee-jerk response that if it's part of a combination, why not? That if it doesn't help, it won't hurt. That's not the case. Vaccines are biological drugs. They can cause harm just like a pharmaceutical drug. In fact, a biological drug--a vaccine--is more likely to cause harm than most pharmaceutical drugs. If the product is good and the animal really needs it, then it should be given, given appropriately, and given as often as needed. If the risk is very low or the product is not very good, then make sure the animal doesn't get it, because the risk may be greater than the benefit.
"From that point of view," Schultz continues, "holistic veterinarians have gotten people to look more carefully at the needs of the animal, to think twice about the value of the products used almost as a routine and frequently without much thought given as to why the product is being used, and if it's doing what it's supposed to do. Very often, those individuals are not looked upon with favor, and their views are not popularly held. This is a very difficult situation as you get people on the other extreme who don't want to give any vaccines.
"For the cat and dog," Schultz adds, "vaccine experts have identified those vaccines every cat or dog should receive and how often they are needed. It would be useful for equine vaccine experts to make recommendations for the horse."
The Road Ahead
Experts are continuing to push such vaccination issues as improved efficacy, better delivery methods, and tailored protocols.
At the University of Saskatchewan, researchers are assessing vaccine efficacy, particularly against equine influenza. "We have been doing this through the use of experimental challenges, by conducting studies to look at the serologic response of horses given a variety of equine vaccines, and by conducting field studies to examine vaccine efficacy in the face of natural disease," says Townsend. "We've learned a lot over the past 10 years, but perhaps the most interesting has been the marked variation in the immune response of horses given different vaccines and the marked variation of response of individual horses and horses of different ages to any one vaccine."
As to the future, Townsend says he believes regulatory agencies will require vaccine manufacturers to provide solid evidence of vaccine efficacy. "As an increasing number of vaccines are shown to be efficacious, those vaccines already on the market, but not supported by efficacy data, should gradually disappear from the scene."
Researchers at the University of Kentucky continue to work on a variety of projects, including improving the strangles and influenza, and finding methods for preventing equine infectious anemia (EIA), equine protozoal myeloencephalitis (EPM), leptospirosis (the cause of abortion, stillbirth, neonatal infection, and recurrent uveitis), and equine herpesviruses 1 and 4.
"The ideal is to prevent the young horse from becoming infected with herpesvirus," says Timoney. "If you can stimulate an antibody that will block the entry of the virus, then you'll reduce the risk of permanent infections that are so typical of the herpesvirus."
He says work continues on genetically engineered vaccines to be given intranasally or orally. "There's possibly some future for DNA vaccines," Timoney says, "but the problem is the mode of administration of the DNA vaccine, because currently they either have to be injected or blasted in under high pressure, and it's often difficult to get a very good antibody response in the horse." He hopes that researchers will investigate efficacy when two or three different intranasal vaccines are administered at the same time.
University of Wisconsin researchers continue to investigate edible and DNA vaccines, the use of alternative vectors that can deliver the antigens of two or three different viruses in a single vectored virus, the biology of the equine immune system, and better protection against equine herpesvirus. Schultz predicts that new vaccines, whether they are needed or not, might be developed to prevent Lyme disease and equine infectious anemia (EIA). Lunn foresees the development of mucosal adjuvants to make vaccines work better, better delivery methods for vaccines, an increased interest by vaccine manufacturers to improve efficacy, and changes in USDA regulations concerning scientific data that proves efficacy.
Private practitioners Ward and Holland also have a few predictions. Holland perceives that manufacturers will develop vaccine lines for foals and also move away from combination vaccines to strategies where vaccinations are staggered over several months and given one at a time. Ward has the same hope. "I think more veterinarians are really going to look at the individual situation, the age, and the overall health of the animal in order to make vaccination recommendations on the individual rather than just blanketing all the horses with injections that they may or may not need."
In truth, when it comes to vaccines, the protocol issue of what to give, when to give it, and to whom it is given, might become a hotter topic than new and under-development drugs.
"In the last few years, a great many questions have been asked about the types and frequency of vaccinations given to children and companion animals," Townsend says. "I am not aware that the horse has been a particular focus for these questions, but logically, that will come with time. I predict that we will see less emphasis upon the concept of a routine program for horses and more effort put into using vaccination programs to achieve maximum protection at the time of the greatest risk of disease."
An Alternative Approach
Madalyn Ward, a DVM (Austin, Texas) who utilizes holistic veterinary approaches including homeopathy, acupuncture, and chiropractic in her private practice, has concerns with vaccination protocols as they stand now. “Over-vaccinating creates an imbalance in the immune system,” she says. “In some horses, over-vaccinating can have a suppressive effect, while in others it over-stimulates the immune system. I work on show horses. I go through the barn, and they’re doing really well and not having any problems. Then I come back and they’re not working well, they don’t have a good attitude, and they’re tight and tense. Turns out they had their vaccinations within a month or so. The acupuncture points that are sore on these horses are often related to the points associated with the immune system.”
She questions whether chronic allergies, respiratory problems, laminitis, and hypothyroidism are related to imbalances in the immune system caused by vaccines. “Part of the problem with the vaccines is the adjuvants they include may cause toxicity in addition to the effect on the immune system. When you have mercury and aluminum included as an adjuvant, the horse may react to those as toxins. As far as I’m concerned, the only vaccines that have been consistently effective and have not caused much trouble for healthy individuals are the vaccines for tetanus and encephalitis.”
About the Author
Marcia King is an award-winning freelance writer based in Ohio who specializes in equine, canine, and feline veterinary topics. She's schooled in hunt seat, dressage, and Western pleasure.