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Disease causing organisms have at least two distinct effects on the body. The first effect is very obvious: we feel sick, exhibiting symptoms such as fever, nausea, vomiting, diarrhea, rash, and many others. Although the second effect is less obvious, it is this effect that generally leads to eventual recovery from the infection: the disease causing organism induces an immune response in the infected host. As the response increases in strength over time, the infectious agents are slowly reduced in number until symptoms disappear and recovery is complete.

Obviously, a live, virulent organism cannot be used as a vaccine because it would induce the very disease it should prevent. Therefore, the first step in making a vaccine is to separate the two effects of disease causing organisms. In practice, this means isolating or creating an organism, or part of one, that is unable to cause full blown disease, but that still retains the antigens responsible for inducing the host's immune response. This can be done in many ways. One way is to kill the organism using formalin; vaccines produced in this way are called "inactivated" or "killed" vaccines. Examples of killed vaccines in common use today are the typhoid vaccine and the Salk poliomyelitis vaccine.

Another way to produce a vaccine is to use only the antigenic part of the disease causing organism, for example the capsule, the flagella, or part of the protein cell wall; these types of vaccines are called "acellular vaccines." An example of an acellular vaccine is the Haemophilus influenzae B (HIB) vaccine. Acellular vaccines exhibit some similarities to killed vaccines: neither killed nor acellular vaccines generally induce the strongest immune responses and may therefore require a "booster" every few years to insure their continued effectiveness. In addition, neither killed nor acellular vaccines can cause disease and are therefore considered to be safe for use in immunocompromised patients.

A third way of making a vaccine is to "attenuate" or weaken a live microorganism by aging it or altering its growth conditions. Vaccines made in this way are often the most successful vaccines, probably because they multiply in the body thereby causing a large immune response. However, these live, attenuated vaccines also carry the greatest risk because they can mutate back to the virulent form at any time. Such mutation would result in induction of the disease rather than in protection against it. For this reason, attenuated vaccines are not recommended for use in immunocompromised patients. Examples of attenuated vaccines are those that protect against measles, mumps, and rubella. Immunity is often lifelong with attenuated vaccines and does not require booster shots.

Some vaccines are made from toxins. In these cases, the toxin is often treated with aluminum or adsorbed onto aluminum salts to decrease it's harmful effects; after such treatment the toxin is called a "toxoid." Examples of toxoids are the diphtheria and the tetanus vaccines. Vaccines made from toxoids often induce low level immune responses and are therefore sometimes administered with an "adjuvant" - an agent which increases the immune response. For example, the diphtheria and tetanus vaccines are often combined with the pertussis vaccine and administered together as a DPT immunization. The pertussis acts as an adjuvant in this vaccine. When more than one vaccine is administered together it is called a "conjugated vaccine." Toxoid vaccines often require a booster every ten years.

Another way of making a vaccine is to use an organism which is similar to the virulent organism but that does not cause serious disease, such as Jenner did with his use of the relatively mild cowpox virus to protect against the similar, but often lethal, smallpox virus. A more recent example of this type of vaccine is the BCG vaccine used to protect against Mycobacterium tuberculosis. The BCG vaccine currently in use is an attenuated strain of Mycobacterium bovis and requires boosters every 3 - 4 years.

In addition, biotechnology and genetic engineering techniques have been used to produce "subunit vaccines" - vaccines which use only the parts of an organism yet which stimulate a strong immune response. To create a subunit vaccine, researchers isolate the gene or genes which code for appropriate subunits from the genome of the infectious agent. This genetic material is placed into bacteria or yeast host cells which then produce large quantities of subunit molecules by transcribing and translating the inserted foreign DNA. It is important to note that these subunit molecules are encoded by genetic material from the infectious agent, not from the host cell's genetic material. These "foreign" molecules can be isolated, purified, and used as a vaccine. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease.

Vaccines are effective in preventing disease not only in individuals, but also in communities. This type of protection is called "herd immunity." When a disease spreads from one human to another, it requires both an infected individual to spread it and a susceptible individual to catch it. Herd immunity works by decreasing the numbers of susceptible people. When the number of susceptible people drops low enough, the disease will disappear from the community because there are not enough people to carry on the catch-and-infect cycle. The greater the proportion of vaccinated members of the community, the more rapidly the disease will disappear. This is the reason that school children are often required to be vaccinated before attending school. This required vaccination has resulted in the marked decrease of many once-common diseases including pertussis (whooping cough), polio, smallpox, and others. Look for the story of the Polio Vaccine in a future Classic Collection chapter. Viva la Vaccine!

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