Yellow Fever Vaccines: The Success of Empiricism, Pitfalls of Application, and Transition to Molecular Vaccinology



In 1951, Max Theiler was awarded the Nobel Prize in Medicine and Physiology for the development of yellow fever vaccine. The discovery phase of Theiler’s research preceded the prize by only about 20 years, during which time his vaccine against yellow fever had been put into wide-scale use in Africa and South America, and tens of thousands of yellow fever deaths had been averted. After smallpox vaccine, which had been discovered some 135 years before, yellow fever was the first human vaccine to be used at a population level for control of a major epidemic disease. Yellow fever vaccines were developed during an early stage in the history of virology, using empirical methods. Approximately 50 years later, research was initiated on the molecular basis of attenuation; progress is briefly reviewed here. The history of yellow fever vaccines provided a number of important paradigms for vaccine development in general (Table 1).


Rabies Virus Yellow Fever Yellow Fever Virus Smallpox Vaccine Avian Leukosis Virus 



Dr A. Barrett kindly shared unpublished data on yellow fever vaccine and parental strain molecular comparisons and insights as to their relevance. Dr V. Deubel assisted in finding, photographs of Drs Mathis and Laigret in the Pasteur Institute archives. Dr F. Rey, Harvard Medical School, kindly provided the figure showing the location of yellow fever 17D virus mutations in the crystal structure of the flavivirus E protein dimer. The author is indebted to the Rockefeller Archive Center, North Tarrytown, NY and the Francis A. Countway Library of Medicine, Boston, MA for photographs of yellow fever researchers.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Kleiner Perkins Caufield & ByersCambridgeUSA

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