TLRs as Targets to Develop Novel Adjuvants
Şefik Ş. Alkan
from: Advanced Vaccine Research Methods for the Decade of Vaccines (Edited by: Fabio Bagnoli and Rino Rappuoli). Caister Academic Press, U.K. (2015) Pages: 187-218.
This chapter starts with a summary of our current understanding of innate immunity, which is the rapid responding arm of the immune system. Innate cells recognize microorganisms via molecular sensors collectively called pattern-recognition receptors (PRR). These evolutionarily conserved sensors consist of four families based on their molecular structures: C-type lectin receptors, NOD-like receptor, and RIG-I-like receptors and Toll-like receptors (TLRs). We will focus on the latter, as TLR agonists are molecules most advanced as vaccine adjuvants. Various degrees of information are available about TLR (TLR2-TLR9) agonists that are under development for the treatment of infectious diseases and cancer: while some are at very early stage, many are in clinical trials and a few are approved as vaccine adjuvants. Decades of TLR research have taught us several lessons. Just to name a few: There is variation in the cellular distribution of TLRs in different species, which makes the translation of animal data into the clinic difficult; simultaneous delivery of TLR agonist and the antigen is more efficacious; multiple TLR activation produces much better adjuvant effects. Equipped with these lessons, we are not far from utilizing multiple TLR agonists as adjuvants in 21st century vaccines against infectious diseases and cancer read more ...