There is reasonable evidence that both cross-priming and direct transfectio
n of antigen-presenting cells (APCs) play a role in induction of immune res
ponses by DNA vaccines. It is not known which mode is more important for pr
iming cytotoxic T cell responses, but both are sufficient and neither alone
is necessary. Hence, a rational strategy for increasing DNA vaccine potenc
y would be to facilitate both pathways. With regard to cross-priming, a bet
ter understanding of the nature of the antigen transferred and the molecule
s/cells involved may suggest ways to design DNA vaccines to enhance this pa
thway. With respect to transfection of APCs, certain DNA formulations or de
livery systems may be able to target APCs for increased DNA uptake. Other c
onsiderations include recruitment of APCs to the site of DNA injection and
manipulation of these cells to ensure the proper activation state far primi
ng immune responses. The burgeoning scientific literature in these areas in
dicates that much effort is currently being directed toward these goals.