TLR, NLR and other modulators as infectious disease vaccine adjuvants

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. Introduction Vaccination has been an extremely powerful tool for preventing infectious diseases. Eradication of smallpox and the dramatic reduction in polio and measles throughout the world represent the most significant successes of vaccination to date. However, infectious diseases remain a leading cause of death worldwide. Traditional vaccines have mainly consisted of live attenuated pathogens, whole inactivated organisms or inactivated bacterial toxins. The development of more advanced and effective vaccines to combat infectious diseases, such as influenza, HIV, tuberculosis and malaria is a major goal of modern medical research. However, these new generation vaccines are usually based on recombinant proteins, and although safer, they are often less immunogenic than traditional attenuated or