Defending Against Disease
- Jan 1, 2005
Editor's Note: This is the first installment in a 12-part series of articles on vaccinations of horses.
Of all the medical advances in the past couple of centuries, the one that might be the most remarkable is also the one we're most likely to take for granted. The simple pinprick of an intramuscular injection taking less than 10 seconds protects our families, our pets, our horses, and ourselves from diseases that once meant certain death. In a flash, there are no more worries about the horrors of diphtheria, rabies, tetanus, or equine encephalomyelitis. All from a few ccs of vaccine.
Perhaps we are so casual about vaccination because it's so familiar. In grade school, most of us learned the story of Edward Jenner, who in 1796 deduced that milkmaids exposed to cowpox, a relatively benign disease, seemed to be immune to the far more virulent smallpox. Jenner might in fact have been borrowing knowledge from more ancient sources--there is some indication that medical practitioners in the Middle East had known for centuries how to immunize patients against smallpox with a small amount of pus from a cowpox vesicle.
Smallpox, which had wreaked untold misery on the human race for millennia, became the first disease against which humans were immunized--and in the 20th Century, the first disease to be officially eradicated from the face of the earth.
A century after Jenner, Louis Pasteur advanced our knowledge of vaccines another giant leap by discovering, quite by accident, that viruses that had been killed or altered by exposure to heat or chemicals might still confer lasting immunity. He injected chickens with a preparation of fowl cholera that had been left out on the lab bench overnight and had dried out. Not only did the chickens not develop the disease from the injections, but when exposed to infected birds, they remained healthy. Pasteur eventually followed up on this revelation by creating groundbreaking vaccines against anthrax and rabies.
By the end of the 19th Century, humanity had gained protective immunization against plague; diphtheria, pertussis (whooping cough), and tuberculosis vaccines followed in the early 1900s.
It wasn't long after vaccination started to become accepted in human medicine that researchers started applying that knowledge to horses. A team of researchers at the University of Kentucky were likely the first. In 1914, they came up with an equine vaccine against a form of contagious abortion after isolating salmonella bacteria from aborted fetuses. Although it wasn't a very safe or effective vaccine, it was notable as a first try.
The same team followed that up in 1917 with a far more successful equine antitoxin against botulism, based on antitoxin research that had been developed just a few years earlier by a team investigating human diphtheria. The same process also yielded a tetanus antitoxin in 1928.
With the development of a new tetanus toxoid for humans in the 1930s (a breakthrough that saved thousands of lives in World War II), vaccine research blew wide open. While products for equines have always lagged a little behind their human counterparts, the pharmaceutical industry has remained reasonably progressive. Today we consider it routine to vaccinate against a vast array of life-threatening diseases, including rabies; tetanus; botulism; Eastern, Western, and Venezuelan encephalomyelitis; West Nile virus; and Potomac horse fever. We also vaccinate against some diseases that are not usually life-threatening, but might take valuable recovery time away from our horses (such as influenza, equine herpesvirus strains I and IV, strangles, and rotavirus).
Since the science was first sorted out, horses have been inextricably linked to vaccine development. Early on they were the natural choice for researchers studying the effects of experimental vaccines, and large enough to produce quantities of antitoxin, when their immune systems were properly stimulated, for human vaccines against diphtheria during the first World War. Recently, horses have actually enjoyed priority over humans in terms of the development of vaccines against West Nile virus, and the innovative technologies used to formulate those fast-tracked equine vaccines will undoubtedly benefit humans.
Vaccines confer disease resistance by the same process that occurs every time an antigen (a foreign protein, or part of a protein) enters the body's tissues. The immune system reacts to all sorts of antigens, from living pathogens (bacteria, viruses, protozoa, and fungi) to pollens and particles in the air. The immune response is a vastly complex mechanism with multiple defenses, and its share of weaknesses, much like any modern-day army. But the familiar goal is to vanquish the invader and maintain (or return the horse to) good health.
As a fringe benefit, once the immune system recognizes an invader, it is much better prepared to defend itself against any further incursions by that invader, thereby (usually) giving the horse some degree of immunity (sometimes long-term, sometimes only for weeks or months, depending on the disease and the vaccine formulation).
The idea of a vaccine is to get the immune system to mount a response against a pathogenic invader while saving the horse from suffering disease symptoms that at best are uncomfortable and inconvenient, and at worst are fatal. In essence, vaccines give the immune system a heads-up about a possible future invader, and they give it time to design the best possible defense with the minimum deleterious effects on the horse.
The goal of vaccine developers is the same now as it was 100 years ago: To isolate the disease-causing organism, grow it in a laboratory situation, render it non-infective, purify it, mix it with carriers called "adjuvants" that enhance its immune-stimulating properties while causing as few side effects as possible, and make it available in an easy-to-administer format. Injectable vaccines are the ones we're most familiar with, but there are also oral vaccines and formulations that are sprayed on the inner surfaces of the respiratory passages.
Two types of immune responses are called into play when a vaccine enters the horse's system. First, there's the humoral response, in which antibody levels in the blood increase. There's also a cell-mediated response, in which disease-fighting white blood cells, or phagocytes, are summoned to destroy foreign agents. It's the humoral response that is generally most important in the fight against re-infection, but with some diseases, cell-mediated response is also key.
In order to understand how vaccines manipulate disease-causing products, it's helpful to be able to picture the enemy. Viruses and bacteria come in a wide variety of shapes, each with its own immune challenges, but all have an outer coat studded with surface proteins (parts of which stimulate the immune response) and an inner core of genetic material. The aim of a vaccine is to get the horse's immune system to recognize the pathogen's unique surface proteins as "foreign" and mount an attack response, without allowing the inner genetic material to trigger disease or multiply inside the host.
Achieving a balance between safety and effectiveness has always been the main challenge in vaccine formulation. Over the last couple of hundred years, there have been several improvements in strategy that have made vaccines far more dependable than they once were. The evolution goes something like this:
Attenuated "Live" Vaccines--Early vaccines often conferred immunity at a price. Because they contained virus or bacteria that were weakened, but alive, they provoked an excellent, long-lasting immune response. But sometimes they triggered the disease itself--a mild case if you were lucky, a full-fledged case if you were not. Vaccines for canine distemper in dogs and red measles in humans were originally of this type, but "attenuated live" vaccines are rarely used in the Western hemisphere today for either horses or humans if there is an alternative available. (One exception is the oral polio virus vaccine for humans, which because of its ease of administration is especially suited to mass immunization programs.)
Toxoids--A variation on the attenuated live vaccine is the toxoid, which is formulated not with live pathogens, but with their toxic by-products. Tetanus and botulism, for example, tend to kill because the bacteria responsible for the disease release highly toxic compounds into the animal's system. Rendered non-toxic by chemical processes, these toxoids, when introduced to the body, can trigger an immune response similar to that seen with attenuated live viruses. One of the earliest discoveries in vaccine research, toxoids are still routinely used to protect against tetanus, botulism, and other clostridial infections.
Killed Pathogens--A vaccine made with killed organisms is far safer than the attenuated live version, but it must be delivered by injection. Antigenic proteins on the surface of the dead pathogens are still able to launch the process of immunity, but the invaders are completely inactivated and pose no danger to the recipient. The down side? The immune response provoked by a killed vaccine is sometimes less complete--or shorter-lasting--than that stimulated by an attenuated vaccine. So these preparations generally depend on the addition of an adjuvant to enhance the long-term immunostimulating effects of the killed virus, and recruit additional immune-cell armies to create a more thorough response.
Adjuvants have much to do with a vaccine's effectiveness, and pharmaceutical companies often closely guard their "recipes" for adjuvants. Some of the ingredients that might be present are mineral or vegetable oils, mineral salts, and saponins (emulsifiers that break oil-based solutions into droplets and give the vaccine a time-release quality).
Recombinant Vaccines--One 21st Century approach to immunization is the recombinant vaccine, so named because it's based on advances in gene manipulation techniques. Recombinant vaccines might feature only surface proteins of a disease-causing virus or bacterium--fragments just complete enough for the immune system to recognize and attack the invader.
Others are gene-deleted vaccines, in which the pathogen has been tampered with to eliminate the genes that cause disease, but retain the ones that trigger the immune response.
Then there are viral vector vaccines, which use recombinant technology to piggyback an immunity-provoking gene onto an harmless virus, so that it masquerades as a pathogen. (A very successful oral rabies vaccine for wildlife, used in bait drops in rabies-infested areas like Texas, Oklahoma, and Ontario, is created this way.)
The advantage of a recombinant vaccine is that it doesn't contain any intact copies of the pathogen--alive or dead--so it's extremely safe, and it can still stimulate good immunity. Merial Limited's Recombitek West Nile virus vaccine is the first formulation of this kind to be made commercially available for horses.
Naked DNA Vaccines--Vaccine researchers have recently found that introducing only the genetic nucleic acids (the components of DNA or RNA) of the pathogen can sometimes confer immunity. This was something of a surprise because these nucleic acids are not generally recognized by the immune system as foreign. But, when strange DNA is introduced to the body, it's taken up by cells that make proteins encoded by that DNA. The immune system then responds to the cells with the foreign proteins by rallying the troops, which confers immunity to the horse.
"The Centers for Disease Control believes that 'naked DNA' will be the basis of most vaccines in the future," says Kevin Hankins, DVM, MBA, an assistant professor at Kansas State University and field veterinary consultant for Fort Dodge Animal Health. "They see it as a better technology, with some significant advantages. There's no vector with a naked DNA vaccine, so there's no risk of infection."
Safety is just one of the advantages of a DNA vaccine. Scientists acknowledge that DNA can be highly purified and does not seem to trigger autoimmune reactions (when the body recognizes its own cells as "not self" and initiates an immune response to destroy them). Furthermore, it's easy to handle, with a long shelf life and no requirement for refrigeration (a major plus for Third World situations). And because DNA is easy to manipulate, vaccines could be easily and inexpensively modified to keep up with mutations and make it to the market faster than the current crop of killed vaccines.
Finally, according to Hankins, "The CDC is hoping it might be effective against diseases we haven't had much success fighting with conventional vaccines."
If the idea of injecting foreign DNA and encouraging its uptake into your horse's cells sounds alarming at first, Hankins offers reassurance. "The DNA in the host cells isn't going to replicate because what's being used is not the whole DNA strand. It just stimulates immunity to those specific antigens, and the cells get destroyed in that process. It's important that people realize this is not the same as genetic engineering. It's not even in the same ballpark."
One of the challenges with DNA vaccines is finding the best method of delivery. The goal is to promote the uptake of the DNA material into cells--and while intramuscular injections have been used, researchers are exploring other avenues, including spraying the vaccine on mucous membranes, or even firing microscopic gold pellets coated with nucleic acids into the skin via a "gene gun." Ultimately, we might be able to inject a string of genes from different organisms and protect against a whole series of diseases all at once.
There are currently no naked DNA vaccines on the market for horses, but it's no secret that they are in development and coming soon to a veterinarian near you.
Reminding the Immune System
DNA vaccines might be the wave of the future, but for now, most of the vaccines we use for horses are the killed-organism type. When a horse is vaccinated against a disease for the first time with an inactivated (killed) virus product, his antibody titer--the level of antibody against that particular virus in the bloodstream--keeps rising for several weeks afterward. The practice of giving a "booster shot," a repeat dose two to four weeks after the original injection (while the titer is still on its way up), ensures the maximum number of immune cells with "memory" are jolted into action for the best possible humoral immune response.
Immunity doesn't last forever. It tends to diminish over time if the horse has no further exposure to the pathogen. So, it's necessary to "remind" the immune system of the danger periodically. The majority of equine vaccines are given on a yearly basis to ensure the antibody titer stays high. Some need to be administered more often; vaccines for influenza, for example, might be repeated every three months. Immunity dissipates more quickly with killed vaccines; those made with attenuated live organisms tend to confer longer-lasting protection.
It's suspected that many equine vaccines might actually confer immunity for longer than a year, but most pharmaceutical companies don't do duration-of-immunity studies--it's both expensive and difficult to measure what qualifies as sufficient immunity. Researchers have yet to answer the thorny question: How much response is enough?
Admittedly, pharmaceutical companies are motivated to sell vaccine, and thus are not likely to investigate whether dosages can be given less often, but the yearly booster does have a less mercenary rationale: It helps you establish a routine and keep track of which boosters are needed. Longer intervals might mean boosters are forgotten. (For example, human vaccinations for tetanus are administered at least every 10 years. Do you remember when you had your last tetanus shot?)
Some vaccines are more effective than others. Those protecting against influenza, equine herpesvirus (rhinopneumonitis, or "rhino"), strangles, and Potomac horse fever are among those that confer something less than 100% immunity, or have to be administered more frequently (often four to six times a year) to provide protection.
The reason? Viruses are sneaky critters with a talent for mutation, and sometimes the mutations change the surface proteins to the point where an immunized body no longer recognizes them as the enemy.
Flu viruses are notorious mutants (although less so for horses than for humans), and even the most up-to-date vaccine cannot possibly protect against all the various strains in the environment. Your horse might be fully protected against several flu strains and still fall victim to one not included in the vaccine formulation. Or he could contract another respiratory virus, like EHV, and exhibit identical symptoms, leading you to blame his symptoms on a failed flu vaccine. You often don't know which disease you're really dealing with.
Furthermore, the vaccines might be conferring as much immunity as they can; most researchers feel that the natural immunity a horse might acquire from contracting and overcoming an infection lasts no longer than the immunity he acquires through vaccination.
Finally, the realities of the pharmaceutical industry mean that by the time a vaccine hits the market, its formulation might already be outdated. Because horses make up a relatively small chunk of the veterinary drug market, it's less profitable for companies to formulate new versions of equine vaccines than to research new ones for cattle or swine. And even when a new formulation for horses is designed, it must still go through years of testing, followed by a long wait in line for licensing, before it lands in your veterinarian's hands.
That's not to say research isn't continuing at a relatively vigorous pace. Companies are continually working on new methods of growing and purifying vaccines to lessen the risk of side effects. Older vaccines, for example, often contained virus grown in chicken eggs. The resulting formulations sometimes contained proteins that triggered allergic responses. Today, viruses are usually grown in purified cell culture media in the lab. Adjuvants are also more highly purified than in the past, and as a result they are more effective and less irritating to the horse.
Taking a Hard Look
Vaccination isn't a perfect process, but it's a lot better than the alternative, say most experts. Over the past couple of centuries, vaccines have saved countless lives and have had incalculable economic impact the world over. Improved sanitation and hygiene have also contributed to the improved health and life spans of humans and horses, of course, but not all disease declined with the advent of indoor plumbing.
Polio is one example of a disease that increased in frequency and virulence when improved sanitation began to allow more people to crowd into urban areas. (Since the virus is shed in fecal material, it's even thought by some researchers that high-tech flush toilets spread polio through the air!) Although less than 1% of children exposed to the virus contracted the paralyzing form of polio, it was still enough to put tens of thousands of North Americans in wheelchairs and iron lungs in the first half of the 20th Century. When Jonas Salk finally came up with an effective vaccine in the early 1960s, it was considered a revolution. (As a direct result of the Salk and Sabin vaccines, polio outbreaks now occur in only a few isolated pockets of the world, and it has been almost completely eradicated in industrialized nations.)
Are we, as some have claimed, weakening the horse's immune system by bombarding it with boosters? The jury is still out on this question, but there is little hard evidence to suggest we are over-vaccinating and doing harm. (More on this debate later in our series.) Rarely do horses suffer localized or systemic allergic responses to vaccines with repeated exposure, but the reaction often comes from the adjuvant rather than the virus itself. A change of brand often takes care of the problem.
Even more rarely, they might experience life-threatening anaphylactic reactions. Is the incidence of allergic response on the rise? Most researchers say not. Those horses who do suffer them are generally older individuals with long exposure to the vaccine--horses which, in another time without that vaccine, might not have survived long enough to exhibit an allergic response.
Severe reactions to vaccines are extremely unusual, largely because attenuated live vaccines are almost never used in horses today. Recombinant or DNA vaccines, the direction the industry is taking, have a particularly wide safety margin. Researchers and veterinarians agree that the danger posed by exposure to deadly diseases such as tetanus, encephalomyelitis, or botulism is far greater than the risk of a vaccine reaction. These are, after all, products that are used safely in millions of horses every year.
We might be circumventing the natural course of evolution by vaccinating our horses, but that's of course true of almost all of our equine management practices. Would it be better to allow our horses to be exposed to, and overcome, disease as nature intended? This theory might be valid if all equine diseases were nothing but a nuisance. But several of them can be deadly; some, like rabies, have no other possible outcome. And some of the safest and most effective vaccines are those that protect against the most horrific disease. To fail to protect your horse against such scourges is not only to risk personal heartbreak, it could put your neighbor's horses at risk as well. That's not to mention the fact that some equine diseases are transmittable to other species, including humans.
In an age where most of us have never witnessed a case of rabies, tetanus, or EEE, it can become easy to see the prevention as worse than the disease, but one only has to read the descriptions of these diseases from a few scant decades ago to be reminded of just what we don't want our horses to suffer.
Perhaps the most dangerous thing about vaccines is that we sometimes expect them to work miracles. It's important to remember that they are merely a tool in the control of infectious disease, not a panacea. Just as crucial as vaccination are sound management practices such as controlling exposure and spread of disease.
Over the next 11 months, we'll bring you much more information about equine vaccines, their pros and cons, risks and realities, with the help of a panel of experts from both academia and industry. Stay tuned for all the vaccine vital statistics.
LEARNING MORE ABOUT VACCINATIONS
- Rabies, Tetanus, Botulism, February 2005
- West Nile Virus, March 2005
- Other Encephalitides, April 2005
- Influenza, May 2005
- Herpesviruses, June 2005
- Strangles, July 2005
- Vaccines Under Trial, August 2005
- Management Strategies for Vaccination Efficiency, September 2005
- Vaccination Schedules for Pregnant Mares, October 2005
- Schedules for Young Horses, November 2005
- Schedules for Mature Horses, December 2005
About the Author
Karen Briggs is the author of six books, including the recently updated Understanding Equine Nutrition as well as Understanding The Pony, both published by Eclipse Press. She's written a few thousand articles on subjects ranging from guttural pouch infections to how to compost your manure. She is also a Canadian certified riding coach, an equine nutritionist, and works in media relations for the harness racing industry. She lives with her band of off-the-track Thoroughbreds on a farm near Guelph, Ontario, and dabbles in eventing.
POLL: EPM Experiences