Although empirical vaccine development was highly successful, it has now re
ached its limits. Vaccines are only efficacious against those pathogens whi
ch are primarily controlled by antibodies. Protection against many infectio
us agents, however, strongly depends on T lymphocytes. Thus, novel vaccines
have to stimulate the combination of T lymphocytes that is required for an
optimum protective immune response. Although identification of antigens re
mains crucial, novel vaccine design also needs to consider the best way of
introducing these antigens to the immune system. Intracellular antigen comp
artmentalisation, the early cytokine milieu and the appropriate surface exp
ression of co-stimulatory molecules are of major relevance for understandin
g how novel vaccines could induce a protective immune response mediated by
T lymphocytes. Intracellular bacteria are controlled by T lymphocytes and e
fficacious vaccines against these pathogens are not available yet. In this
treatise, two experimental vaccination strategies will be described in more
detail. These encompass recombinant vaccine carriers expressing, and naked
DNA constructs encoding, heterologous antigens. Both vaccination strategie
s proved to be protective in the model of experimental listeriosis of mice.