Linking vaccine adjuvant mechanisms of action to function

Vaccines deliver an immunogen in a manner designed to safely provoke an immune response, leading to the generation of memory T and B cells and long-lived antibody-producing plasma cells. Adjuvants play a critical role in vaccines by controlling how the immune system is exposed to the immunogen and providing inflammatory cues that enable productive immune priming. However, mechanisms of action underlying adjuvant function at the molecular, cell, and tissue levels are diverse and often poorly understood. Here, we review the current understanding of mechanisms of action underlying adjuvants used in subunit protein/polysaccharide vaccines and mRNA vaccines, discuss where possible how these mechanisms of action link to downstream effects on the immune response, and identify knowledge gaps that will be important to fill in order to enable the continued development of more effective adjuvants for challenging pathogens such as HIV and emerging threats.