The need for a novel generation of vaccines

Although empirical vaccine development was highly successful, it has now reached its limits. Vaccines are only efficacious against those pathogens which are primarily controlled by antibodies. Protection against many infectious 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 remains crucial, novel vaccine design also needs to consider the best way of introducing these antigens to the immune system. Intracellular antigen compartmentalisation, the early cytokine milieu and the appropriate surface expression of co-stimulatory molecules are of major relevance for understanding how novel vaccines could induce a protective immune response mediated by T lymphocytes. Intracellular bacteria are controlled by T lymphocytes and efficacious 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 strategies proved to be protective in the model of experimental listeriosis of mice.