Adjuvants can be incorporated into vaccines to enhance the magnitude, functionality, breadth and durability of antigen-specific immune responses.

A deeper mechanistic understanding of how adjuvants in licensed vaccines regulate innate and adaptive immunity can help advance vaccine design.

Challenges include variations in adjuvant formulations, lack of sufficiently detailed knowledge on vaccine delivery sites, target cells and innate signalling pathways.

Systems vaccinology provides a means to progress adjuvant development away from trial and error towards a more rational approach.

Adjuvants are a miscellaneous range of molecules and materials that can enhance the magnitude, functionality, breadth and durability of immune responses. Despite the multiplicity of compounds with adjuvant properties, less than a dozen are in clinical use in vaccines against infectious diseases. While many factors have contributed to their slow development, among the major challenges are the high safety and efficacy standards set by current adjuvants in human vaccines and our limited understanding of how adjuvants mediate their effects. This review outlines why it is so difficult to elucidate their mechanism of action, highlights areas that require in-depth research and discusses recent advancements that are revitalising adjuvant development. It is hoped that a fuller understanding of adjuvant sensing, signalling and function will facilitate the design of vaccines that promote sustained protective immunity against challenging bacterial and viral pathogens.

Vaccine

Adjuvant

Antibody

T cell

B cell

cell mediated immunity

mechanisms of action

PRRs

PAMPs

DAMPs

© 2022 The Author(s). Published by Elsevier Ltd.