From empiricism to rational design: a personal perspective of the evolution of vaccine development

Nat Rev Immunol. 2014 Jul;14(7):505-14. doi: 10.1038/nri3694. Epub 2014 Jun 13.


Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIDS Vaccines / immunology
  • Adjuvants, Immunologic / pharmacology
  • Communicable Disease Control*
  • Glycoconjugates / immunology
  • History, 20th Century
  • History, 21st Century
  • History, Ancient
  • History, Medieval
  • Humans
  • Influenza Vaccines / history
  • Influenza Vaccines / immunology
  • Malaria Vaccines / immunology
  • Plague Vaccine / history
  • Plague Vaccine / immunology
  • Smallpox / immunology
  • Smallpox / prevention & control*
  • Tuberculosis Vaccines / immunology
  • Vaccination / history*
  • Vaccines / history*
  • Vaccines / immunology
  • Vaccines, DNA / history
  • Vaccines, DNA / immunology


  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Glycoconjugates
  • Influenza Vaccines
  • Malaria Vaccines
  • Plague Vaccine
  • Tuberculosis Vaccines
  • Vaccines
  • Vaccines, DNA