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Introduction To Immunology: Part I- The Role Of And Problems With Vaccines PDF Print E-mail
Written by Myra Ehrman, RN, BA, BS, MScN   
Original Article Written by Myra Ehrman, RN, BA, BS, MScN, on behalf of the Health Education Committee, CKCSCC. Originally Published in The Cavalier King Charles Spaniel Club of Canada Newsletter, "Quotes", in March, 1996

In the fall, 1995, several club members residing in southern Ontario had the opportunity to attend a seminar on immunology organized by the Cavalier Fanciers of Southern Ontario club. The seminar was given by Delsworth G. Harnish, Ph.D., who is Associate Professor, Departments of Biology and Pathology, McMaster University. That seminar, and questions that arose following the death last spring of a 14 year old Cavalier shortly after receiving her annual immunizations, provided the incentive for this article.

We'll start with a Glossary of basic medical terms, taken from Miller - Keane's Encyclopedia and Dictionary of Medicine and Nursing, to facilitate understanding of the content which follows.

Antibody - a protein that is produced in the body in response to invasion by a foreign agent (antigen), and that reacts specifically with it. Antibodies are part of the body's natural defense against invasion by foreign substances. Each antibody is effective only against the particular antigen that stimulates its production.

Antigen - any substance not normally present in the body, which, when introduced into it, stimulates production of an antibody that reacts specifically with it. Antigens are almost always of protein composition; for example, the structures of bacteria and viruses and the toxins they elaborate are protein.

Immunity - resistance of the body to the effects of a harmful agent, such as pathogenic microorganisms (viruses and bacteria, for example) or their toxins (poison produced by living organisms). Immunity occurs as a result of the antigen-antibody reaction that takes place whenever a foreign agent or its product enters the bloodstream.

Acquired immunity is that which results from antibodies not normally present in the blood; called also induced immunity.

Active immunity is produced by natural or artificial stimulation so that the body produces its own antibodies. It may be produced either by an attack of the specific disease or by introduction of vaccines or toxoids by injections.

Cellular immunity is acquired immunity (usually to an infectious agent) in which the role of phagocytic cells (cells circulating in the blood which destroy microorganisms or harmful cells) is predominant.

Humoral immunity is acquired immunity in which the role of circulating antibody is predominant.

Natural immunity is an innate resistance to disease due to the presence of antibodies occurring normally in the blood.

Passive immunity is a state of nonsusceptibility to certain microorganisms produced by injection or ready-made antibodies present in immune serum (anti-serum) or gamma globulin (a plasma protein developed in response to invasion by harmful agents).

Vaccination - inoculation with weakened or dead microorganisms to develop immunity to a specific disease.

Vaccinations of course are given in order to prevent the development of infectious diseases. Usual modes of transmission from one animal to another are through contact with infected urine, feces, and other bodily secretions; or by inhaling infected droplets in the air. It is also possible for an animal to become infected via transmission in the genital tract when dogs mate, or if there is a break in the skin and there has been contact with spores.

There are three primary types of vaccines currently in use.

A) Attenuated or modified live - Attenuation is the act of thinning or weakening. To be effective, the antigen should be as similar to living organisms as possible. Attenuated organisms have their ability to produce disease greatly reduced, but they are still able to replicate themselves. In fact, they must replicate after inoculation to produce enough antigen to induce an immune response. The process to produce attenuated vaccines commonly subjects the organisms to unusual conditions, or culturing in unfavorable media or at an unfavorable temperature.

Canine distemper and rabies vaccines are produced through multiple passages in eggs. Most commonly, cells from the species to be vaccinated are used to reduce the likelihood of side effects when prolonged tissue culture is the method of production. One example in The Merck Veterinary Manual- Seventh Edition is that canine distemper virus is repeatedly cultured in canine kidney cells, although it normally affects lymphoid cells.

The goal is to produce a genetically stable agent which will not produce disease, but this is difficult to achieve, and reversion to disease-producing status can be a serious risk.

Positive attributes of attenuated vaccines are that they tend to produce a better and long-lived immune response; they provide local immunity; and fewer immunizations are required, resulting in lower cost. Negative attributes include their decreased safety (they can revert to virulence - ability to produce disease, and may be shed into the environment) and their ability to induce suppression of the immune system. Modified live vaccines are also very sensitive to improper storage.

B) Killed - Organisms are most often killed through application of chemicals which destroy the nucleic acids of the organisms while leaving the protein antigens intact. Photoinactivation is an emerging technology. Heating alone is usually unsatisfactory.

Killed vaccines are safe with respect to the likelihood of inducing disease or causing contamination, and are relatively easy to store. On the other hand, higher doses are needed to be effective, there is a higher cost associated with multiple vaccinations, and they produce a weaker immune response which is of shorter duration as well. They also need to be combined with another substance (adjuvant) in order to be truly effective.

C) Subunit - If that portion of an organism that stimulates an immune response can be identified and isolated, it can be used as a vaccine by itself. The Merck Veterinary Manual- Seventh Edition cites as an example when a cloned b subunit of E coli bacteria enterotoxin is used as a vaccine; b subunits stimulate immune response and function as effective toxoids. The b gene is then cloned, linked with a powerful promoter, and introduced into a non-disease producing strain of E coli. The subunits on their own are not infectious, and allergic reactions to nonessential parts of the vaccine are reduced. On the other hand, the cost is quite high, and weaker immunity may be provided overall. Subunit vaccines have some of the same advantages and disadvantages of killed vaccines. Currently subunit vaccines are not often used in veterinary medicine because of their higher cost and lack of proven efficiency.

Considerations for pregnant bitches and young puppies

The immune systems of pregnant bitches is less responsive than normally, so as not to reject puppies as foreign objects. That means the bitch is more susceptible to viral and bacterial infection than usual. A wise owner will not bring a pregnant bitch to dog shows or other activities where many unfamiliar dogs who could be carrying infections congregate. Special care should also be taken regarding owners' shoes and other clothing not coming into contact with the pregnant bitch upon the owners returning from dog events themselves. A prudent owner will also disinfect any grooming tables or other equipment used at a show prior to bringing them back into a house where a pregnant bitch lives. Live virus vaccines (attenuated or modified live) should not be given to pregnant bitches because of potential harmful effects on the fetus, such as fetal resorptions, abortions, or resulting birth defects. No pregnant bitch should be vaccinated until this has been discussed with your veterinarian. Females who have not been immunized within a year should be given a booster for DHLPP (canine distemper, hepatitis, leptospirosis, parainfluenza, and parvovirus) prior to being bred. If it is deemed necessary to vaccinate a pregnant bitch, the dam may be vaccinated during the later stages of pregnancy with the doses being timed so that peak antibody formation occurs at the time colostrum is being produced.

Once the bitch whelps, the first milk the puppies receive is called colostrum. Puppies receive passive immunity from the dam through the colostrum, and are best able to absorb the immunity through their intestines during the first 24 to 36 hours after birth. It makes sense that dams vaccinated within a few months have the highest levels, and the length of protection for the puppies is dependent upon the antibody level when the puppies were born. The maximum length of protection for the puppies is 16 weeks, and maternal antibody is degraded at a constant rate.

It is worth noting that one of the most common problems regarding immunization is maternal antibody interference with active immunization. If a neonate does not receive maternal immunity, its chances of survival are greatly reduced. However, maternal antibody interference can also account for vaccine failure, probably because the maternal antibody binds to the vaccine in such a way that the vaccine is cleared from the body before it is able t o stimulate an immune response.

New information on maternal antibody effect on canine parvovirus has resulted in recommendations for a different vaccination schedule than has been previously been used. It has been demonstrated that as many as 20% of dogs at 18 weeks of age have a sufficient amount of maternal antibody to prevent successful canine parvovirus (CPV) immunization. The current recommendation calls for puppies to receive three to four immunizations given at regular intervals between the ages of 6 and 22 weeks. Unless the last immunization is adminstered at 22 weeks of age or older, a certain percentage of dogs will remain unprotected until the next immunization, which will probably be given as the annual booster immunization. And once again it should be observed a careful owner will restrict or carefully control the puppy's visits to group dog activities outside the home until the full cycle of initial immunizations is complete. It should also be remembered that any vaccination is not likely to be effective until at least 3-7 days after immunization has occurred.

Failures and adverse consequences of vaccination

Vaccine failures have occurred. For example, inactivation of modified live vaccine before or immediately after inoculation will result in failure. Sometimes vaccines may contain the wrong strain of organisms or the wrong antigens, or the manufacturing method may have destroyed the important components. A vaccine manufactured correctly may fail due to incorrect method of administration (under the skin when it should have gone in the muscle, for instance); improper storage; mixing with another incompatible vaccine; use of antibiotics in conjunction with a live bacterial vaccine; chemical sterilization of syringes; or excessive use of alcohol on the skin. Also, if the animal has already been incubating the disease before vaccination, the vaccine will not confer protective properties. The immune response cannot be assured to be equal for all dogs; the response of most animals will be average, a few will be excellent, and a small number will be poor. If the immune response has already been suppressed, such as in an animal suffering from a heavy infestation of parasites, a high degree of malnutrition, or extremes of cold and hot temperatures, then vaccine failures can also happen.

Risks associated with vaccination include residual susceptibility to the disease originally vaccinated for; contamination with other harmful substances (such as introducing bacteria on a non-sterile syringe); allergic responses; disease in animals with suppressed immune systems in which modified live vaccines are used; neurological complications; and harmful effects on the fetus. Some vaccines may sting when administered and cause discomfort to the animal. Also, vaccines, like any antigen, may provoke one of four types of hypersensitivity reactions. These hypersensitivity reactions will be described more fully in the next "Quotes" Health Watch article on Introduction to Immunology Part II - Allergies and Hypersensitivity Reactions.

A good rule of thumb is that only healthy, clinically normal dogs should be vaccinated.

Prodigy On-Line computer service had a Pets Bulletin Board. The veterinarian in charge of this Bulletin Board was asked about adverse effects of immunizations on older dogs. He replied, "...this is a more general but more confusing and controversial issue. There are many working on the questions raised, but little hard information that helps guide us in this area. Though some veterinarians are quite positive that "over" vaccination in certain breeds is responsible for many different syndromes, other researchers are much less certain or are opposed to those ideas. Dr. Jean Dodds...has been a champion of the search for associations with autoimmune dysfunction in pure bred dogs and has consistently pointed out the possible relationship with use of multivalent mlv (modified live) vaccines. Her research and observations are not without considerable controversy, however, so it is difficult to know how to advise as a practicing veterinarian in such areas. I think we do need much more research."

Annual vaccinations or not?

The last point to be made for now is that the practice of annual vaccinations was started many years ago without consideration for scientific validity or verification. Once exposed, immunity to viruses persists for years or for the life of the animal, while successful vaccinations for bacterial disorders produces an immunologic memory that remains for years and allows the animal to develop a protective secondary response when exposed to the same organisms. Currently only the immune response to toxins requires boosters, and no toxin vaccines are being used for dogs. There are many rabies vaccines which provide a 3-year duration of immunity, for example. It is probable that most annual vaccinations take place because: 1) it is a way for the veterinarian to have the animal come in on a regular basis for physical examination; and 2) it is the law in many communities. If enough people in the club feel strongly it is time to work with members of the scientific community to advocate for changes in legal requirements, this could be an issue the club chooses to follow up over the next few years.

Disclaimer: Your veterinarian is the most qualified person to answer all of the questions you have about your pet's health. Nothing in this article should be construed as medical advice regarding any individual animalís condition.

© Copyright April 11, 1999.
 
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