Polynucleotide immunization has been described as the Third Revolution in V
accinology. Early studies suggest the potential benefits of this form of im
munization including: long-lived immunity, a broad-spectrum of immune respo
nses (both cell mediated immunity, and humoral responses) and the simultane
ous induction of immunity to a variety of pathogens through the use of mult
ivalent vaccines. Using a murine model, we studied methods to enhance and d
irect the immune response to polynucleotide vaccines. We demonstrated the a
bility to modulate the magnitude and direction of the immune response by co
-administration of plasmid encoded cytokines and antigen. Also, we clearly
demonstrated that the cellular components (cytosolic, membrane-anchored, or
extracellular) to which the expressed antigen is delivered determines the
types of immune responses induced. Since induction of immunity at mucosal s
urfaces (route of entry for many pathogens) is critical to prevent infectio
n, various methods of delivering polynucleotide vaccines to mucosal surface
s have been attempted and are described. Expansion of studies in various sp
ecies, using natural models, should be extremely helpful in demonstrating t
he universality of this approach to immunization and more importantly, accu
rately identify parameters that are critical for the development of protect
ive immunity. (C) 1999 Elsevier Science B.V. All rights reserved.