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Basic Vaccinology

By: Randall J. Berrier, DVM. Senior Vice President Scientific Affairs Colorado Serum Company

Vaccines have proven to be a major scientific advancement for people and animals for over a century. Vaccination is the most efficient, practical and cost effective means of controlling infectious diseases via prophylaxis. The enormity of the benefit from vaccines is hard to comprehend and is one of the biggest reasons, if not the biggest reason we, as a society, currently enjoy our relative good state of health.

Vaccination has been responsible for the eradication of small pox in people and Rinderpest in livestock across the globe; the elimination of hog cholera from North America; and the control of diseases such as foot and mouth disease, pseudorabies, rabies, Brucella and anthrax would not have been possible without the use of effective vaccines.

The general principle behind the use of vaccines is to introduce a modified and safe version of a given pathogen into an animal host which induces an immune response that will be protective to the animal in the future if and when it encounters a natural exposure to this pathogen.

There are two basic methods by which an animal may be made immune to an infectious disease: 1. Passive immunity - This produces immediate but temporary resistance by transferring antibodies from a resistant animal to a susceptible animal. 2. Active immunization - This involves exposure of antigens (foreign substance/vaccine) to an animal so that it responds by developing its own protective immune response.

Passive immunization requires that antibodies be produced in a donor animal by active immunization and that these antibodies are then given to susceptible animals in order to confer immediate but short lasting protection. Serum containing these antibodies may be produced against a wide variety of pathogens.

Active immunization occurs when an animal is exposed to a foreign substance/antigen naturally or when administering antigens (vaccine) to an animal and it responds by developing its own protective immune response. There is a non-specific (cell mediated) immune response and a humoral immune response which generates specific B lymphocytes that produce specific memory cells that make antibodies.

With active immunity re-immunization or exposure to infection will result in a secondary immune (antibody) response. The disadvantage of active immunization is that protection is not conferred immediately. The advantage of active immunization is that once it is established, it is long lasting and capable of re-stimulation.

Passive immunization requires that antibodies be produced in a donor animal by active immunization and that these antibodies are then given to susceptible animals in order to confer immediate but short lasting protection. Passive immunization occurs when the dam passes on antibodies to the newborn through the first milk or colostrum. Passive immunization can also be conveyed through serum antibodies.

Serum containing these antibodies, (called serum antibodies, antiserums or antitoxins) may be produced against a wide variety of pathogens. In livestock some of the most important roles of antiserums is in the protection against toxigenic organisms such as Clostridium tetani or Clostridium perfringens.

Antiserums made in this way are commonly produced in horses by a series of immunizing injections. The toxins of these Clostridia are proteins that can be denatured and made nontoxic by treatment with formaldehyde. This type of vaccine is known as a toxoid.

After “hyperimmunizing”, these horses are bled when their antibody levels are sufficiently high and the serum antibody fraction is separated from the blood, then processed and dispensed for use in susceptible animals.

Serum antibodies can be introduced into a recipient animal by injection subcutaneously and, or intramuscularly, depending on the product, and in some cases intravenously.

The main advantage to passive immunity (through colostrum or serum antibodies) is instant immunity to particular diseases. The disadvantage is immunity only lasts for 6 – 8 weeks from colostrum in most livestock (but up to 6 months in horses) and only 10 – 14 days in the recipient from serum antibody, so repeat doses may be needed in the case of these antiserums.

Active immunization has several advantages compared to passive immunization mainly from the prolonged period of protection that is achieved and the recall from boosting (from re-vaccination or natural infection).

The challenge for vaccine manufacturers: The perfect vaccine should illicit a high protective immune response with the absence of adverse side effects

Traditionally there have been two types of vaccines through the years: 1. Live/modified live vaccines and 2. Killed vaccines.

Modified live vaccines usually infect host cells and undergo replication. These infected cells then process endogenous (inside the cell) antigen. In this way the vaccine antigen triggers an immune response. Usually a cell mediated immune response and some degree of humoral (antibody) immune response is achieved with ML vaccines. The virulence of live vaccines must be reduced so that they will create a protective immune response without creating disease. The process of reducing virulence is called attenuation. Attenuation of live vaccines can be achieved in a number of different ways; adapting organisms to growth in unusual conditions so that they lose their adaption to their usual host, genetic manipulation, growing viruses in cells or species to which they are not naturally adapted and prolonged growth in tissue culture in cells that the virus is not adapted to are just a few examples of how attenuation is achieved.

Disadvantages to using live vaccines include: 1. Less stability – more sensitive to temperature excursions. 2. Safety – greater risk of contamination or reversion to virulence. 3. Possible risk to humans from accidental exposure (e.g. - needle sticks). Advantages to using live vaccines are: 1. Fewer inoculating doses are usually required. 2. Adjuvants are usually not unnecessary. 3. Less chance of hypersensitivity (allergic reactions). 4. Induction of interferon (a type of non-specific cell mediated immunity). Some examples of live or ML vaccines are the bovine virus combination vaccines (IBR, BVD, PI3, BRSV vaccines), Anthrax Spore Vaccine, Ovine Ecthyma Vaccine, RB51 Brucella abortus Vaccine and many others.

For inactivated or killed vaccines there are different ways of inactivating antigens for vaccine production, most common is formaldehyde, but others include alkylating agents (ethylene oxide, ethyleneimine, acetylethleneimine, and beta-propiolactone), irradiation, iodination and others.

Disadvantages to using killed vaccines include: 1. The tendency to induce a lesser immune response so they usually require an adjuvant (see below) to make up for this. 2. Local injection site reactions that the adjuvants can cause. 3. Multiple dosing (booster) is usually required which increases the risk of hypersensitivity reactions.

Advantages of inactivated vaccines include: 1. More stable in storage. 2. Safety - they will not cause disease through residual virulence and they are unlikely to contain contaminating organisms. Some examples of inactivated vaccines include the Clostridial vaccines (7-Ways and 8-Ways), Tetanus and CD&T toxoid, rabies and many others. All of these mentioned vaccine examples have a really good track record for efficacy.

Immunologic adjuvants are added to vaccines (usually inactivated vaccines) to stimulate the immune response to the target antigen, but do not in themselves confer immunity. Examples include: Aluminum phosphate, Aluminum hydroxide, Freund’s incomplete and complete adjuvant, Saponin, Mineral oil based, Squalene and many others.

The most common route of administering vaccines is through injection subcutaneously or intramuscularly. There are some vaccines that are administered intranasally (e.g. - Inforce-3 in Cattle, some Influenza vaccines for pigs and horses). These intra-nasal vaccines are MLV vaccines that help stimulate local cell mediated immunity (interferon). There are also some oral vaccines for pigs (Enterisol) and dogs (Bronchi-Shield, Vanguard) that also stimulate local cell mediated immunity.

Autogenous vaccines can also be made when necessary. When a farm or ranch encounters an organism that is unique or a variant that there is no commercial vaccine for, an autogenous vaccine may be useful. Autogenous vaccines are made from a sample of organisms taken from infected animals on a given farm and is made specifically for use at that particular location. There are USDA regulated laboratories that make autogenous vaccines.

More modern vaccine technology include the following USDA classifications: Antigens generated by genetic engineering, Genetically attenuated organisms, Live recombinant organisms (Subunit vaccine, Gene deleted vaccines, Vectored virus vaccines, Other - Naked DNA, RNA vaccines).

Lastly, every serial of a licensed USDA biologic (vaccine, bacterin, toxoid, serum antibody, etc.) must pass potency, purity (sterility), and safety testing prior to release and the USDA Center for Veterinary Biologics randomly retests repository samples sent in by every company for every serial to confirm results. Because of these quality control measures and regulatory oversight, getting a “bad batch” of vaccine is nearly impossible.

Lastly, the slight risks of adverse reactions following vaccination should always be viewed in light of the great numbers of animals that have been protected from deadly and costly diseases from vaccination. Stop and think what the world would be like without vaccines.

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