Challenges and responses in human vaccine development.

Human vaccine development remains challenging because of the highly sophisticated evasion mechanisms of pathogens for which vaccines are not yet available. Recent years have witnessed both successes and failures of novel vaccine design and the strength of iterative approaches is increasingly appreciated. These combine discovery of novel antigens, adjuvants and vectors in the preclinical stage with computational analyses of clinical data to accelerate vaccine design. Reverse and structural vaccinology have revealed novel antigen candidates and molecular immunology has led to the formulation of promising adjuvants. Gene expression profiles and immune parameters in patients, vaccinees and healthy controls have formed the basis for biosignatures that will provide guidelines for future vaccine design.