The field of DNA vaccines has undergone explosive growth in the last few years. As usual some
historical precursors of this approach can be d- cerned in the scientific literature of the
last decades. However the present state of affairs appears to date from observations made
discreetly in 1988 by Wolff Malone Felgner and colleagues which were described in a 1989
patent and published in 1990. Quite surprisingly they showed that genes carried by pure
plasmid DNA and injected in a saline solution hence the epithet naked DNA could be taken up
and expressed by skeletal muscle cells with a low but reproducible frequency. Such a simple
methodology was sure to spawn many applications. In a separate and important line of
experimentation Tang De Vit and Johnston announced in 1992 that it was indeed possible to
obtain humoral immune responses against proteins encoded by DNA delivered to the skin by a
biolistic device which has colloquially become known as the gene gun. The year 1993 saw the
publication of further improvements in the me- ods of naked DNA delivery and above all the
first demonstrations by several groups of the induction of humoral and cytotoxic immune
responses to viral antigens expressed from injected plasmid DNA. In some cases protection
against challenge with the pathogen was obtained. The latter result was - questionably the
touchstone of a method of vaccination worthy of the name.
