• knowledge of clinical signs and symptoms of the disease to allow differentiation from similar syndromes

• identification of the pathogen and its major characteristics, including strains and serotypes, their infectivity, their virulence, their antigenicity, and the nature of essential immunogens

• the existence of specific techniques for cultivation of the pathogen

• identification of nonhuman models of infection

• knowledge of the human immune response to the pathogen, including the duration and type of response (e.g., serum antibody, mucosal antibody, or cell-mediated immunity)

• definition of the target population.

All aspects of the knowledge base that involve technical feasibility must be reassessed frequently: a vaccine not foreseeable today may become a reality in the future because of one unexpected development in the laboratory. Such developments are especially likely in the fields relevant to vaccine development because modern biotechnology has only begun to be explored.

The criteria for selecting candidates for accelerated vaccine development do not address the general question of which vaccines are most needed in the developing world or its particular regions. For some diseases that impose major burdens, the knowledge base is insufficient to allow consideration of accelerated vaccine development by NIAID. Nevertheless, portions of the analysis described in this report can be applied to these disease problems to gain useful information about long-term goals and potential benefits. The description of disease burden considerations in Chapter 4 may be especially helpful in this regard.

The committee hopes that the selection of candidates for accelerated vaccine development will not divert funds from long-term basic research programs. For these programs, the scientific merit of the research proposal should continue to be the dominant criterion for funding.

The committee believed that its major contribution to establishing priorities would be the clear explication of a logical method for this task and that it probably could never satisfy all potential critics with its choice of candidates for assessment. As noted in Chapter 3, if a candidate is omitted from the full assessment, no conclusions should be made regarding its position in the priority rankings relative to the assessed contenders. When the prospects for vaccine control of disease were reasonable, however, the committee tried to include in the full analysis those candidates generally recognized in the developing world and the United States as major disease problems.