Towards the systematic discovery of immunomodulatory adjuvants

Adjuvants potentiate immune responses, reducing the amount and dosage of antigen needed for protective immunity. Adjuvants are particularly important when considering subunit, epitope-based, or other more exotic vaccine formulations that lack significant inherent immunogenicity. While innumerable adjuvants are known, only a handful are licensed for human use: principally alum, and squalene-based oil-in-water adjuvants. Alum, the most commonly used, is suboptimal. There are many varieties of adjuvant: proteins, oligonucleotides, drug-like small-molecules, and liposome-based delivery systems with adjuvant activity being perhaps the most prominent. Like poisons, adjuvants function via several mechanisms. Many plausible alternatives have been proposed. Focussing in particular on the discovery of small-molecule adjuvants, in the following we give a brief and fairly synoptic overview of adjuvants and their discovery.