Table 1. Needs and challenges for the rational design of vaccines.

Subunit Vaccine Component	Focus of Future Developments	Benefit Toward Rational Design
Antigens	Knowledge on the most effective immune response against a particular pathogen	Selection of antigens and formulations evoking those responses
	Antibody epitope database	Basis for development of computational prediction tools
	Prediction of sequences that should be excluded due to (i) risk of autoimmune responses, (ii) immune escape by antigenic drift, and (iii) responses to only selected strains or clades of the pathogen	Design of antigens capable of eliciting potent cross-reactive immune responses with minimal risk for side effects
	Continuous survey and registration of evolving pathogenic strains and clades	Improved coverage for selected antigens
	Investigation of protein/peptide degradation rules for different vaccination routes	Improved stability of designed antigens
	Extension of MHC allele–peptide complex databases, especially for MHC class II	Increased reliability of epitope prediction with already available tools
Delivery systems	Advancement of nanotechnologies	Improved synthetic delivery systems
	Investigation of mechanisms to overcome preexisting immunity or persistent virus superinfection	Maximizes potential of live vectors derived from pathogens causing common human chronic infections
	Understanding the basis for eliciting memory responses	Design of vaccines triggering long-lasting protection
	Investigation of the interface between innate and adaptive immunity	Exploitation of optimal APC targets and intrinsic adjuvant properties of the delivery system
Adjuvants	Knowledge on the most effective immune response against a particular pathogen	Selection of adjuvants facilitating those responses
	Investigation of vaccination route-dependent adjuvant effects	Optimized use of adjuvants and vaccine design
	Elucidation of molecular mechanisms of adjuvanticity	Optimizes adjuvant use and forecasts potential side effects
	Investigation of the basis of immune stimulation in different population groups	Development of personalized vaccines