Abstract
Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed.
•Live vaccines against human diseases caused by viruses have been very successful.•They have been developed by empirical clinical studies and problems identified in later use.•It can be difficult to balance ability to cause disease and ability to immunise for a strain.•There is currently no reliable basis for predicting success from pure virological studies.•Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.