novel vaccines could be evaluated using assays demonstrating the induction of immunity. Variola proteins expressed from plasmids or in other vectors could be used to detect variola-specific immunity, such as neutralizing antibodies or other viral proteins, or recognition of variola proteins by T cells that mediate cytotoxicity and antigen-specific cytokine release. Nevertheless, confirmatory assessment of the induction of functional protective immunity would require testing using variola virus, and the margin of confidence in the probable efficacy of such vaccines would be enhanced by studies of challenge by variola virus in animal models yet to be developed.
Despite the major obstacles involved, the design of novel vaccines is scientifically feasible, and may constitute a rationale for preserving variola stocks for future use in such an endeavor. From a public health perspective, however, circumstances that would require vaccination of immunocompromised persons might never arise. If an early, limited outbreak were to be detected, it should be possible to protect these individuals and keep them from becoming new source cases by vaccinating a large enough portion of the population to prevent spread of the infection to those who could not be immunized safely. Should a very large-scale, contemporaneous exposure occur, protective isolation would be the only alternative to vaccination. If large numbers of people were placed at risk, protective isolation would not be a practical strategy, and a noninfectious vaccine would be valuable. On the other hand, one can envision an exposure situation evolving so rapidly that immunocompromised patients within the population at large could not be identified and excluded from the vaccine campaign in a timely manner. It is important to recognize that under these conditions, the availability of a novel vaccine safe for high-risk patients would have limited practical benefit.