The live attenuated yellow fever vaccine 17D was found as early as 1936 by M. Theiler of the Rockfeller Foundation. This strain of yellow fever is still the only one used today. The experience acquired with this vaccine has led to various changes in its composition: use of the seed lot system (in 1941) following the accidents observed in Brazil; elimination of human plasma as stabilising agent because of hepatitis B transmission (1942); preparation of a vaccine free of avian leukemia; perfection of a thermostable vaccine (1984). These various successive improvements resulted in one of the most effective vaccines. Over the past years, different ways of improving the vaccine have been envisaged: change of cellular substrate, purifications, development of a new vaccine through genetical engineering. We will review these different approaches in order to gauge their advantages and drawbacks both from a legislative and pharmaceutical point of view. It has been recently suggested that an infected cDNA clone from the 17D strain be used as a yellow fever vaccine or as a gene-vector for other flaviviruses. This most promising approach raises questions, notably ones of security and legislation which we will discuss.
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