Challenge versus natural infection as an index or protection after influenza immunization.

The most important consideration in evaluating an immunization procedure is protection from infection. Protection provided by influenza vaccines can best be determined by large scale field trials and natural infection. However, these are difficult to control and epidemics cannot always be accurately predicted. On the other hand, representative artificial challenge studies can be controlled and are easier to perform. In the studies, reported protection achieved against artificial challenge is compared with protection effected in vaccinees during natural influenza epidemic. Protection rate against artificial challenge with influenza A was 96% when vaccine and challenge viruses were homotypic. When the vaccine strain and challenges virus were heterotypic, protection ranged from 70-100%. Protection rate from infection during a homotypic epidemic was, retrospectively, 95%; while 50-87% protection from influenza illness was achieved during a heterotypic epidemic. In all instances, vaccinees experienced mild, mostly afebrile upper respiratory symptoms, unlike controls who had moderate to severe symptoms, often with fever. Infecting virus was shed more often by unvaccinated controls. Although artificial challenge was performed in healthy young adults, epidemiological results indicate that similar protection can be achieved for children, the elderly or high risk. Thus statistically representative sampling of immunized and non-immunized controls and challenge can be used as a direct indication of vaccine efficacy against natural infection in all populations.