Targeting Pattern Recognition Receptors (PRRs) in Nano- Adjuvants: Current Perspectives

Abstract

Enormous progress in the field of vaccine development has moved the area from traditional vaccines using whole microorganisms to subunit vaccines containing only purified or modified antigenic proteins. The low immunogenic potentials of subunit vaccines compared to live attenuated pathogens, have prompted the research towards developing new adjuvants with the ability to mimic and enhance the innate and adaptive immune responses. Novel adjuvants formulations based on the discovery of pattern recognition receptors (PRRs), the main class of innate immunity sensors have recently gained interest. The major family of PRRs called Toll-like receptors (TLRs), which are expressed by a variety of cells and capable to induce innate immune responses and effective stimulation of transition from innate immune responses to adaptive immune responses. PRR ligands of natural and synthetic origin have been evaluated as potential adjuvants in a variety of applications including vaccine formulations. Apart from this, for generating effective and protective immune responses, targeted delivery of vaccine antigens along with PRR agonists to the desired cells is of great importance. New strategy of delivering vaccine antigens along with adjuvants using proper nano-sized materials has gained much attention during the recent years. Here we review the recent advances regarding PRR-based nano-adjuvants developments, focusing on current nano-materials based delivery system and their applications in biomedical sciences.

Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient In Vivo Immune Responses

“…Given the size (180 ± 5 and 135 ± 7 nm) of the vehicles constructed in our study which are in the size range of pathogens like viruses and small bacteria and the presence of dual TLR agonists on and inside the NPs, this could be considered as an artificial biomimetic approach to resemble pathogen-like molecules harboring artificial PAMPs. During natural infection, most pathogens present multiple PAMPs to initiate the innate immune responses through multiple stimulation of PRRs, resulting in activation of innate and adoptive immune responses ( 4 , 30 ). Therefore, pathogen-mimicking NPs hold great potential as vaccine and adjuvant delivery system due to their ability to induce and enhance cytokine secretion and recruitment of professional immune cells at the injection site as well as stronger humoral and cellular immune responses in vivo ( 35 , 36 ).…”

“…During natural infection, most pathogens encounter with the immune system through multiple danger signals including PAMPs to stimulate multiple PRRs, resulting in a synergistic upregulation of pro-inflammatory cytokines and chemokines and subsequent activation of antigen-presenting cells (APCs). Therefore, the combination of multiple PRRs agonists and proper delivery systems may be a promising strategy in any artificial immunization approach to induce effective immune responses in the context of vaccine-adjuvant development ( 1 – 4 ).…”

Immunogenicity of Different Types of Adjuvants and Nano-Adjuvants in Veterinary Vaccines: A Comprehensive Review

“…TLRs are internal messages that specifically affect DCs and subsequently increase antigen delivery to APCs, directing them to the MHCI and MHCII molecules, where more interferon and cytokines are produced. Then, by stimulating TLRs on DC and B cells, synergistic antibody responses were observed [ 105 , 106 ]. Due to intracellular localization, processed APCs deliver antigens in the cytosol through MHCI and MHCII molecules.…”

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery

“…Interaction between PAMPs and PRRs initiates a cascade of intracellular signaling pathways that promotes the production and secretion of pro-inflammatory cytokines such as type I IFN, TNF-α, IL-1 and IL-6 and chemokines including IL-8 and RANTES [ 160 ]. The inflammatory responses lead to the migration of mature DCs to lymph nodes and initiate adaptive immune responses leading to an immunological memory [ 161 , 162 ]. Adjuvants interact with cellular PRRs and stimulate innate immunity.…”