PRR Ligands Scanning

Non-living vaccines (Subunit Vaccine, Totally Synthetic Vaccine and DNA and RNA Vaccine) are more stable than live attenuated vaccines (Live Attenuated and Killed Vaccine), but generally exhibit limited immunogenicity. Adjuvants can be used to increase the magnitude of protective adaptive immunity in response to pathogen-associated antigens. Recently developed adjuvants usually include substances that stimulate pattern recognition receptors (PRR), which are essential components of innate immunity required for activating antigen-presenting cells (APC) and serve as a bridge between innate and adaptive immunity. Almost all PRRs are potential targets for adjuvants. Creative Biolabs is a world leader in vaccine services and provides PRR Ligands scanning service for vaccine adjuvantation to meet different customer's demand.

Activators of PRRs, such as TLR agonists, can improve the immunogenicity of a given vaccine and are therefore considered as promising molecules for the development of new vaccine adjuvants. In addition, PRR agonists can be used as an alternative to prophylactic or therapeutic agents to combat infectious diseases. Early innate immunity also plays an important role in controlling tumor progression, so PRR agonists are also actively pursued as anti-tumor properties and therapeutic potential as cancer vaccine adjuvants.

How Does Pattern Recognition Receptor (PRR) Work?

Early innate immunity is the first line of defense against the invasion of pathogens. Early pathogen recognition plays a key role in the subsequent triggering of the proinflammatory response to invading pathogens and coordination of pathogen-specific adaptive immune responses simultaneously. Adjuvants can stimulate innate immunity by interacting with cellular pattern recognition receptors (PRRs), which can detect pathogen-associated molecular patterns (PAMPs), distinct, evolutionarily conserved pathogen structures. PRRs trigger complex signaling cascades with the engagement of PAMP, resulting in the production of an appropriate set of cytokines and chemokines, including interferons (IFNs), the enhancement of antigen presenting capacity, and migration of DCs to lymphoid tissues, in which DC interact with T cells and B lymphocytes to elicit and form an adaptive immune response.

PPR Agonists Used as Vaccine Adjuvants

Several PRRs have been identified, including Toll-like receptors (TLRs), Nucleotide binding oligomerization domain NOD-like receptors (NLRs), C-type lectin receptors (CLRs), Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and Cytoplasmic DNA sensors (CDSs).

Table 1. PPR agonists used as vaccine adjuvant ^[1]

PRR Receptor Class	RLRs	TLRs
Natural Ligand	pppRNA, dsRNA	LPS	Flagelin	dsRNA	ssRNA	CpGDNA
Natural or Synthetic agonists used as Vaccine Adjuvant in Clinic (C) or Clinical Trials (T)	Poly (C) and derivatives (T)	MPLA (C) AS01 (C) AS02 (T) AS04 (C) RC-529 (C)	Flagelin (T)	Poly (C) and derivatives (T)	lmiquimod (T)	CpG-ODNs (T)

Current Application Situation of PPR as Vaccine Adjuvants

Although PRR agonists have significant immunostimulatory activity, there are still some limitations of using such molecules as vaccine adjuvants, such as manufacturing costs, which may limit the global distribution of vaccines. In addition, for intracellular PRR agonists, efficient delivery to target cells is crucial for maximum adjuvant activity, as ineffective internalization will reduce its ability to activate PRR receptors. In currently used adjuvant systems, this problem can be solved by combining with a Delivery System such as a liposome and a nanocarrier, which improve the effect of ligands by promoting their internalization and thereby enhancing their activity.