| Vaccines that contain only killed organisms or subunits will not cause disease and are relatively easy to store. Some live vaccines, conversely, may have a limited ability to cause disease (residual virulence) in vaccinated animals. There is a risk of contamination with unwanted organisms in live vaccines. They also require considerable care in their preparation, storage, and handling to avoid temperature extremes that can affect the organisms. |
As a compromise, the virulence of an organism can be reduced (attenuated) so that it is able to replicate but is no longer pathogenic. Attenuation has traditionally involved adapting organisms to unusual conditions. Bacteria can be attenuated by culture under abnormal conditions, and viruses can be attenuated by growth in species to which they are not naturally adapted. For example, rinderpest vaccine virus has been adapted to tissue culture to produce a safe vaccine. Other examples are adaptation of African horse sickness virus to mice and of canine distemper virus to ferrets, however, vaccines attenuated this way are not commonly used.
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| Vaccine viruses may also be attenuated by growth in alternative media, such as tissue culture or eggs. This has been done for canine distemper, bluetongue, and rabies vaccines. The most common method is prolonged tissue culture. Usually, cells from the species to be vaccinated are used to reduce the problems caused by the administration of foreign tissue. In these cases, the virus is attenuated by growing it in cells that it would not normally infect. For example, canine distemper virus normally infects lymphoid cells, but for attenuation purposes, the virus is repeatedly cultured in canine kidney cells. |
| Attenuation eventually results in the production of a genetically stable, avirulent agent. This may be difficult to achieve, and reversion to virulence is a concern. Rigorous reversion to virulence studies are performed to demonstrate stability of the attenuation. In addition, modern molecular techniques are increasingly used to ensure loss of virulence. |
| For some diseases, related organisms normally adapted to another species can impart limited immunity. Examples include measles virus, which can protect dogs against distemper, and bovine viral diarrhea virus, which can protect against classical swine fever. |
Under some circumstances, fully virulent organisms can be used in vaccination procedures, eg, vaccination against contagious ecthyma (orf ) of sheep. Lambs are vaccinated by rubbing dried, infected scab material into scratches made on the inner thigh, which produces local infection with only limited effects on the lambs; they become solidly immune. Because the vaccinated animals may spread the disease, however, they must be separated from unvaccinated stock for a few weeks.
| Gene-deleted Vaccines: |
Because attenuated organisms may revert to virulence, deliberate deletion of genes associated with microbial or viral virulence is an increasingly attractive procedure. Gene-deleted vaccines were first used against the pseudorabies herpesvirus in swine, eg, development of a vaccine in which the thymidine kinase gene was removed from the virus. Herpesvirus requires thymidine kinase to return from latency. Viruses from which this gene has been removed can infect neurons but cannot replicate and cause disease. This vaccine not only confers effective protection but also blocks cell invasion by virulent pseudorabies virus and prevents development of a persistent carrier state. It is also possible to alter surface antigens so that a virus induces an antibody response distinguishable from that caused by wild strains. This concept is referred to as DIVA, or distinguishing infected from vaccinated animals.
| Live Vectored Vaccines: |
| An alternative method of inducing strong immunity is to place the genes for a protective immunogen in an avirulent “vector” organism. The most widely used viral vectors are poxviruses such as fowlpox, canarypox, and vaccinia. Vectored vaccines are commercially available for avian influenza in poultry, canine distemper, rabies in dogs and cats, West Nile virus infection in horses, and for use in vaccinating wildlife against rabies. These vaccines are free of adverse effects, stable, adaptable to mass vaccination, nonadjuvanted, and like the gene-deleted vaccines, allow for DIVA. They are created by recombinant technology, wherein one or more genes are deleted from the vector and replaced by one or more protective genes from the pathogen. The vector is then administered as the vaccine, and the inserted gene products are produced by the vaccinate’s own body cells when infected by the vector. The vector may be severely attenuated so that it will not be shed from the vaccinate, or it may be host-restricted so that it will not replicate itself within the tissues of the vaccinate. Field data collected on these vaccines indicate strong immunity, limited side effects, and no shedding into the environment when used in a bait and distributed into the habitat of a wildlife species being immunized. |
In the recombinant avian influenza vaccine, the hemagglutinin gene from the influenza virus has been incorporated into a gene-deleted vaccine strain of fowlpox. The immune system of the vaccinate reacts against the poxvirus, and the gene encodes proteins from the influenza virus, inducing protection against both diseases. The vaccine has been shown to be effective in the field against morbidity and shedding of the influenza virus, when used as a primary vaccination. In the recombinant-vectored rabies vaccine, the gene encoding the rabies glycoprotein has been incorporated into an attenuated vaccinia virus. Because this virus is taken up by mammalian cells nonselectively, many different wildlife species can be protected against rabies with this vaccine. Canarypox vector-containing genes obtained from canine distemper virus is now used to immunize dogs, and a similar vector containing the gene encoding rabies glycoprotein is effective in protecting dogs and cats against rabies.
| DNA Vaccines: |
| It is possible to immunize an animal simply by injecting it with bacterially derived DNA coding for an antigen. If the DNA is incorporated into an appropriate plasmid, it is able to express the protective antigen and trigger an immune response. Although no DNA vaccines are currently commercially available, they are likely to enter the veterinary market in the near future in preventative and therapeutic forms. |
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