In the history of vaccine development, key observations have gradually led to our ability to take rational approaches toward the induction of protective immunity to microbial pathogens. The earliest efforts consisted of inoculating lesion material into healthy individuals resulting in the then inexplicable prevention of the development of similar disease. Centuries later, after researchers found that microscopic forms were responsible for the major human diseases such as tuberculosis and smallpox, vaccines consisting of inoculating weakened or attenuated organisms were developed. The discovery of the cell populations that mediate antibody and cellular immune responses, followed by the identification of the cytokine mediators of cellular immunity and the ability to identify, isolate, purify, and produce antigenic molecules of various pathogens has permitted a rational approach toward vaccine development. Perhaps no disease model has been more widely used to understand the roles...

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