Original Article

Journal of Clinical Immunology

, Volume 27, Issue 4, pp 363-371

Toll or Toll-Free Adjuvant Path Toward the Optimal Vaccine Development

  • Ken J. IshiiAffiliated withExploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency (JST), Osaka UniversityDepartments of Host Defense, and Molecular Protozoology, The 21st Century Center of Excellence (COE), Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University Email author 
  • , Shizuo AkiraAffiliated withExploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency (JST), Osaka UniversityDepartments of Host Defense, and Molecular Protozoology, The 21st Century Center of Excellence (COE), Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University Email author 

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Abstract

Successful vaccines contain an adjuvant component that activates the innate immune system, thereby eliciting antigen-specific immune responses. Many adjuvants appear to be ligands for toll-like receptors (TLR), which are thus promising targets for the development of novel adjuvants to elicit vaccine immunogenicity. However, recent evidence suggests that some adjuvants activate the innate immune system in a TLR-independent manner possibly through other pattern recognition receptors and signaling machinery. In particular, newly identified intracellular retinoic-acid-inducible gene (RIG)-like receptors, NOD-like receptors, or even as yet unknown recognition machinery for the adjuvant may regulate TLR-independent vaccine immunogenicity. To develop optimal vaccines, it will be critical to understand how TLR-dependent and TLR-independent innate immune activation, by various adjuvants, control the consequent adaptive immune responses to vaccine.

KEY WORDS:

Innate immunity adaptive immunity toll-like receptor (TLR) vaccine adjuvant dendritic cells monophosphoryl lipid A (MPL) outer-surface lipoprotein (OspA) Hib-OMPC NOD desmuramylpeptides (DMP) muramyldipeptide (MDP) complete Freund's adjuvant (CFA) incomplete Freund's adjuvant (IFA) bacille calmette guerin (BCG) flagellin DNA vaccine ICE protease activating factor (IPAF) neuronal apoptosis inhibitory protein 5 (NAIP5) dsRNA Poly-I:C retinoic-acid-inducible gene I (RIG-I) melanoma-differentiation-associated gene 5 (MDA5) IPS-1 ssRNA interferon B-DNA Z-DNA CpG DNA