Towards an evidence based approach for the development of adjuvanted vaccines

•New adjuvants are typically a combination of delivery system and an immune potentiator.•A deeper understanding of innate immunity has helped the discovery of new adjuvants.•Adjuvant discovery and manufacture favor synthetic small molecule immune potentiators.•Aluminum salts (Alum) should remain the benchmark comparator for any new adjuvants.•Omics and systems biology will benefit the clinical development of adjuvanted vaccines. In the last two decades, several vaccines formulated with a new generation of adjuvants have been licensed or approved to target diseases such as influenza, hepatitis B, cervical cancer, and malaria. These new generation adjuvants appear to work by delivering a localized activation signal to the innate immune system, which in turn promotes antigen-specific adaptive immunity. Advances in understanding of the innate immune system together with high-throughput discovery of synthetic immune potentiators are now expanding the portfolio of new generation adjuvants available for evaluation. Meanwhile, omics and systems biology are providing molecular benchmarks or signatures to assess vaccine safety and effectiveness. This accumulating knowledge and experience raises the prospect that the future selection of the right antigen/adjuvant combination can be more evidence based and can speed up the clinical development program for new adjuvanted vaccines.