The technologies utilized to develop vaccines have drawn from advances in virology, bacteriology, immunology and molecular biology. Both the very first vaccine developed by Edward Jenner for smallpox and the most recently-approved vaccine for varicella are examples of live virus vaccines, employing a strain of the DNA virus less virulent than the wild-type virus. In between these two vaccines, a number of other strategies have been successfully employed including attenuation of RNA viruses, inactivating an organism with or without subunit purification, conjugation of polysaccharides to protein carriers, and subunit protein vaccines made by recombinant DNA technology. The successes of these vaccines have resulted in the prevention of untold morbidity and mortality. Indeed, in a study published by the Harvard School of Public Health’s Center for Risk Analysis,’various pediatric vaccines and vaccine strategies have a median cost per life year saved of< $ O compared to a median of $19,000 for medical intervention, and a median of $?, 780,000 for toxin controls.(See TABLE 1 for specific examples drawn from Ref. 1.)

The dramatic efficacy of vaccines coupled with the burgeoning understanding in the relevant scientific disciplines at the cellular and molecular level have raised the expectations of the public and biomedical scientists alike that new vaccines should be easy and straightforward to develop. The rationale for targeting diseases for development of new vaccines (TABLE 2) includes the desire to: increase the efficacy of an existing vaccine (eg, influenza and tuberculosis); increase the safety or perceived safety (pertussis); expand the population of vaccinees, who may require a different antigen (pneumococcal conjugate vaccines); or decrease the number of injections required (hepatitis B). Additionally, as the incidence of certain infections rises (eg, human papilloma virus), or as new diseases emerge (Lyme disease, AIDS) so does the need arise for effective new vaccines. Concomitant with the increased need for, and appreciation of, vaccines, developments in immunology have increased the scientific understanding of how best to generate protective immune responses. For example, the elucidation of the interactions of T cell receptors with antigenic peptides and major histocompatibility complex (MHC) molecules, the mechanisms whereby proteins are processed into epitopes, and the cellular interactions required for development of immune responses occurred recently. Thus the scenario for significant advances in vaccine development has been set: the need for vaccines, the appreciation for their efficacy, and newly discovered research tools for the vaccinologist. This may have been what prompted DA Henderson to proclaim that “the 1990s are going to be the decade of the vaccine,” in 1991 when he was Associate Director of the Office of Science Technology Policy. z