| Vaccines may contain either living or killed organisms. Killed organisms are commonly much less immunogenic than living ones. As a result, vaccines that contain killed organisms or their products usually require the use of adjuvants to increase their effective antigenicity. These adjuvants may, however, cause local inflammation, and multiple doses or high individual doses of antigen increase the risks of producing hypersensitivity. |
| Inactivated vaccines should resemble the living organisms as closely as possible. Chemical inactivation is usually used under conditions that cause minimal change to the antigens. Compounds used in this way include formaldehyde, ethylene oxide, ethyleneimine, acetylethyleneimine, and β-propiolactone. |
While whole killed organisms are economical to produce, they contain many antigens that do not contribute to protective immunity. They may also contain toxic molecules that can provoke adverse effects. Thus, it is often advantageous to use subunits or subcomponents of microorganisms as vaccine antigens.
| Subunit Vaccines: |
| When the immunogenic portion of an organism can be identified, it can be used in a vaccine by itself. These fractions may be derived by purifying individual components of a whole cell culture. Thus, purified tetanus toxin, inactivated by treatment with formalin (tetanus toxoid), is used for active immunization against tetanus. The attachment pili of enteropathogenic Escherichia coli can be isolated, and the purified pilus proteins incorporated into vaccines. The antipilus antibodies thus protect animals by preventing bacterial attachment to the intestinal wall. |
| If quantities of purified antigen cannot be produced economically by fractionation, genetic material that codes for antigens can be isolated by recombinant DNA techniques. This DNA is then inserted into an expression vector such as a bacterium or yeast, which then expresses that protein. Subunit vaccines can then be derived from recombinant organisms into which a foreign gene from a specific pathogen has been inserted. The recombinant organism is propagated, and the protein encoded by the inserted gene is harvested, purified, and administered as a vaccine. An example of a subunit vaccine is one directed against the cloned subunit of E coli enterotoxin. Subunits are immunogenic and function as effective toxoids. The gene has been cloned, linked with a powerful promoter, and transfected into a nonpathogenic strain of E coli . A purified subunit protein vaccine, OspA, encoded by a single gene obtained from Borrelia burgdorferi has been highly effective in protecting dogs against Lyme disease. Recombinant DNA techniques are useful when protein antigens need to be synthesized in large, pure quantities. |
Although antigens may be large molecules, they usually have only a small number of sites (epitopes) that are important in inducing protective immunity. If the structure of a protective antigen is known, its important epitopes may be identified, and their structure analyzed and then artificially synthesized. In theory, these synthetic epitopes may then be used in a vaccine if they are large enough to be immunogenic. In practice, they are usually uneconomical to produce commercially.
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