Rationale for development of vaccines

The concept underlying vaccine development is straightforward: application of a harmless derivative of an infectious agent should stimulate the immune system to produce antibodies that protect against that agent.

Introduction of any foreign substance into the body can never be entirely devoid of risks, however, so the prime question to be addressed is whether the benefit can be expected to outweigh the risks. Therefore,

1. the pathogen must be dangerous—an infection with it is associated with a high morbidity and mortality rate, and
2. vaccination will generate robust immunological protection against severe disease.

These requisites were fulfilled in the historic successes of vaccine development against smallpox, tetanus, diphtheria and poliomyelitis. The euphoria created by these scientific milestones caused one decisive fact to be overlooked, however. In all four cases, the agents were transported to their destination in the bloodstream, where they could be captured by the antibodies.