TLR, NLR agonists, and other immune modulators as infectious disease vaccine adjuvants

Abstract

Vaccines based on attenuated or killed viruses and bacteria are highly effective in preventing infection with a range of pathogens, but can have safety issues. Therefore, there is a move towards subunit vaccines based on recombinant proteins or naked DNA. However, protein subunit vaccines are typically poorly immunogenic when administered alone and therefore require co-administration with adjuvants to boost the immune response. For many decades there was very little progress in understanding the mechanism of action of adjuvants, but recently there have been a number of significant breakthroughs in this area. The binding of pathogen-derived molecules to different immune sensors, including Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR) and retinoic acidinducible protein-1-like receptors (RLR), activate important innate immune pathways and provide us with not only an understanding of how current vaccines and adjuvants work, but also provide potential targets for novel adjuvant development.