as six or more); thus, it might be possible to develop a single vaccine that would immunize a person against multiple agents. This area offers much promise for the future of vaccine development.

For all of their potential, however, vaccines should not be viewed as so-called magic bullets for defeating emerging microbial threats. The potential value of vaccination and the speed with which vaccines can be developed depend on many factors. Especially important are the existing scientific knowledge of the agent (or similar organisms), its molecular biology, rate of transmission, pathogenesis, how the human immune system responds to natural infection, and the nature of the protective immunity the vaccine induces.

Successful vaccines were first developed against organisms (such as smallpox and yellow fever viruses) that produce acute infections and generate a natural immune response that protects against reinfection. For such diseases, it was only necessary to induce an immune response through vaccination that was similar to that induced by the natural infection. Bacterial diseases like diphtheria and tetanus, whose clinical effects are the result of exotoxins, were good first targets for vaccine development because of the strong immune reaction stimulated by the toxins. For a number of viral diseases (such as polio), attenuated vaccines, which mimic the wild-type virus's ability to produce protective immunity, have been quite effective.

Vaccine development for other infectious diseases, particularly those caused by protozoans, helminths, and fungi, has proved to be quite difficult, often because the responsible pathogens are able to evade the body's normal immune defenses. In such cases, even natural infection does not always induce protective immunity. In malaria, for example, the protozoa that cause the disease go through a multistage life cycle. At each stage, the antigens exposed to the immune system are different; these changes effectively create a ''moving target" that is difficult for the body, and for vaccine developers, to combat effectively. An additional problem in malaria is that the body is "tricked" into mounting an immune response against noncritical parts of the organism rather than against those parts that are capable of inducing effective antimalarial immunity (Institute of Medicine, 1991a).

Vaccine development may be impeded by economic factors as well as by inherent mechanisms in the pathogens under study. The development of vaccines requires an extensive, up-front investment in research that most vaccine manufacturers (and policymakers) are reluctant to make, since few vaccines are highly profitable and the very strict FDA requirements for proof of a vaccine's safety and efficacy make the risk of failure an important consideration. This reluctance of vaccine manufacturers to invest in research contrasts with the attitude of drug manufacturers, who invest considerable funds in research and development. One reason for the difference may be that, as a group, drugs have a much better record of profitability.



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