Immunostimulatory DNA sequences (ISS) have been shown to promote CTL and Th
1 immune responses to coinjected antigens. This phenomenon can be attribute
d to the capacity of ISS to induce the secretion of type-1 cytokines and to
up regulate costimulatory ligands on antigen-presenting cells. We hypothes
ized that ISS administration prior to antigen administration (prepriming),
via the mechanisms stated above, would Th1 bias immune responses to subsequ
ently injected antigens for an extended period of time. The data presented
show that ISS provide in vivo adjuvant activity for up to 2 weeks after int
radermal or intranasal delivery. Furthermore, the results demonstrate that
ISS prepriming can induce immune responses that are significantly stronger
than with ISS/antigen covaccination. ISS prepriming offers an :alternative
approach to the traditional use of adjuvants (i.e., antigen/adjuvant coinje
ction) and expands the potential clinical applications for ISS. (C) 1999 Ac
ademic Press.