Innate Immune Stimulators

Stimulation of the innate immune system is potentially very important in people with an immature adaptive immune system and vaccination cannot be used to reduce the risk of infection. Creative Biolabs is a world leader in the field of vaccine development who has focused on the vaccine industry for years. The extensive experience and expertise of our scientists enable Creative Biolabs to provide innate immune stimulators related development services.

Adjuvant is a key component of vaccines against infectious disease and cancers because they can further promote the immune response of vaccines. In addition to being used as a part of vaccine, certain adjuvants can also be used as anti-tumor agents for cancer immunotherapy. The mechanism by which adjuvants can promote anti-tumor immunity typically relies on the stimulation of innate immunity by PRR, such as TLR, upon which innate immune cells elicit a robust and sustained adaptive immune response against the tumor.

Because of the lack of effective anti-tumor immunity or the induction of poor immunity, cancer vaccines require much better adjuvants than those currently licensed, including the most commonly used alum and incomplete Freund's adjuvant. Recently, some combinations of innate immune stimulators have shown efficacy superior the common ones, suggesting that the optimal combination of currently available or fully characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy.

TLRs and NLRs are two forms of PRRs expressed by innate immune cells to sense and capture danger signals. Cell surface TLRs (TLR-1/2/4/5/6) sense exogenous pathogens and endolysosomal TLRs (TLR-3/7/9) recognize endogenous ligands. NLRs are cytosolic PRRs and the sensory components of the inflammasome. Both TLRs and NLRs are hardwired receptors that mediate inflammatory process to eliminate noxious sources that compromise tissue homeostasis.

Fig.1 Innate immune response in inflammation. (Nowarski R. 2013)

C-type Lectin Receptors (CLRs) Ligands

C-type lectin receptors (CLRs), such as Dectin-1, Dectin-2, Mincle, CLEC9A, DC-SIGN, and MBL, comprise carbohydrate binding domain. CLRs can recognize various carbohydrate motifs on the microorganism by the calcium-dependent manner. CLRs contain a large family of receptors, whose lectin activity is mediated by conserved carbohydrate recognition domains. Dectin-1 is a specific receptor for β-glucan and can recognize several fungal species, including many human pathogens.

Retinoic Acid-inducible Gene I (RIG-1)-like Receptors (RLRs) Ligands

RLR receptors are cytoplasmic RNA sensors containing caspase activation and recruitment domains and can detect the presence of RNA from a broad range of viruses by the innate immune system. There are three types of RLRs, including RIG-I, MDA5, and LGP2. Polyinosinic-polycytidylic acid (Poly I:C) is one of the synthetic dsRNA molecules that activate innate and adaptive immune components. It mimics viral infections and elicits host immune responses by triggering specific pattern recognition receptors (PRRs).

Stimulator of Interferon Gene (STING) Ligands

Stimulator of interferon gene (STING) plays an important role in the innate immune system and it is the first line of defense against pathogenic invasion of bacteria and viruses. As a central protein in the innate immune response of intracellular DNA, STING has emerged as a hot target for vaccine adjuvants and anticancer drug development. The discovery of potent human STING agonists is expected to revolutionize current cancer immunotherapy.

Toll-like Receptors (TLRs)

Toll-like receptors (TLRs) in particular are widely regarded as key players regulating innate and adaptive immune responses to antigens. Cell surface TLRs include TLR-1, -2, -4, -5, -6, -10, and -11, and intracellular TLRs include TLR-3, -7, -8, and -9. Direct-targeting to TLRs using rationally designed subunit vaccine candidate with built-in TLR agonist has become a hot field of vaccine research and development.

Creative Biolabs is specialized in assisting pharmaceutical clients with every stage of the vaccine discovery services, especially adjuvant selection, and formulation optimization. We have experienced experts and advanced platforms that are able to provide the best quality services and high level of specialized support. If you are interested in our services, please contact us for more details.

Reference

  1. Nowarski R, et al. Innate immune cells in inflammation and cancer. Cancer Immunol Res. 2013, 1(2): 77-84.

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