Figure 1. Issues regarding the development of new vaccine strategies. The Pasteur paradigm is highlighted in bold. Issues in vaccine development that are found in the successful accomplishment of each step are highlighted laterally. On the left: some issues of vaccine development are beyond the challenges involved in following the Pasteur paradigm. The choice of the diseases to be targeted by new vaccine strategies may be influenced by aspects that escape the strictly technical issues and challenges imposed by the pathogen: the market expectations of profit, as well as the costs to the end consumer (either to individual subjects or governments), may limit the availability and usefulness of new vaccine strategies to reduce the burden of infectious diseases. On the other hand, non-infectious conditions, as listed in the text, have been addressed as targets for the development of new vaccines, and the strategies for their development are not covered by the Pasteur paradigm. The genetic variation among human populations may influence vaccine efficacy, as already shown for vaccines currently in use, which may raise the need for specific vaccines for different regions of the world. On the right: even for infectious diseases the steps suggested by the Pasteur paradigm may yield important issues to be overcome during vaccine research and development. Not all pathogens are culturable, rendering strategies such as the use of inactivated or attenuated organisms not applicable to some diseases. When selecting pathogen antigens to be obtained without the need to culture the organism, issues regarding which antigen(s) to choose and the antigenic variation of the pathogen will often need consideration. Inactivated organisms may retain residual virulence that may limit their usefulness in susceptible populations, or may lack antigen determinants or adjuvant properties that are needed for optimal stimulation of a proper immune response to the pathogen targeted. An optimal response to antigen administration is influenced by the delivery systems, vectors and adjuvants of choice, which impact on variables such as route of entry and need of multiple doses. Suitable strategies to assess the efficacy of newly proposed vaccine strategies may also need to be developed, from appropriate animal models to adequate markers of protection that may serve as evaluation endpoints other than the frequency of disease in tested populations.