Poly I:C as Vaccine Adjuvant

Pathogen-associated molecular patterns (PAMPs) are increasingly recognized as a key component of many modern vaccines. Polyinosine-polycytidine (poly-IC), when properly combined with an antigen, can be used as a PAMP-adjuvant to activate a variety of elements of host defense in a pattern similar to viral infection. Creative Biolabs is a leader in the field of vaccine development and the extensive experience and expertise of our scientists enable us to provide development services related to innate immune stimulators, particularly the adjuvant development of Poly I:C.

Polyribosinic:polyribocytidic Acid (Poly(I:C))

Polyinosinic-polycytidic 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). Poly-IC signals primarily through MDA-5 (cytoplasmic receptor) and TLR3 (transmembrane and most endosomal receptor). It is also reported that Poly-IC signals through RIG-I, which appears to be dependent on the length of the dsRNA. Through TLR3 and RIG-I-like receptor (RLR) signaling, poly-IC induces a strong interferon response; expression of cytokines, chemokines, and costimulatory factors; and activation of protein kinase R (PKR), 2', 5'-oligoadenylate synthetase (2,5-OAS) and other dsRNA-dependent systems.

Chemical structure of polyinosinic:polycytidylic acid (sodium salt), colour coded.

Fig.1 Chemical structure of polyinosinic:polycytidylic acid (sodium salt), color coded.

Poly(I:C) Derivatives

The derivatives of Poly(I:C) are also effective adjuvants, such as poly-IC12U and poly-ICLC, of which the mechanisms and potency of immune activation are not identical.

  • Poly-IC12U. To overcome the toxicity problems associated with Poly(I:C) as the mismatches in the molecular skeleton reduce its half-life in vivo, Poly-IC12U, a modified version of poly-IC, was developed. Poly-IC12U has mismatched uracil and guanosine residues, resulting in a shortened half-life and therefore does not elicit antibodies to double-stranded nucleic acids.
  • Poly-ICLC. Poly-ICLC is a synthetic derivative of Poly(I:C) and also contains poly-L-lysine in carboxymethyl cellulose (CMC). It is made by a combination of a poly-I-poly C mixture and poly-L-lysine in CMC. Poly-ICLC is not just a mixture, but a new molecule that cannot be broken down into its original components. It not only retains the biological activity of the parent Poly(I:C) but also has a significantly increased resistance to nuclear solubilization.

Structure of poly-IC derivatives. Structure of (A) poly-ICLC and (B) poly-IC12U.

Fig.2 Structure of poly-IC derivatives. Structure of (A) poly-ICLC and (B) poly-IC12U. (Martins KA. 2015)

Poly(I:C) as Cancer Vaccine Adjuvant

As the objective response rate of cancer vaccine is low, the right choice of adjuvant may improve efficacy. Poly I:C and its derivatives have been used as vaccine adjuvants for cancer immunotherapy for decades, based on their ability to enhance innate immunity and adapt to immune responses and alter the tumor microenvironment. These synthetic immune risk signals enhance vaccine-induced anti-tumor immune responses and contribute to tumor elimination in animal tumor models and patients. Recent studies have shown that poly I:C can directly induce apoptosis in several types of tumor cells, thus providing a new treatment for cancer treatment.

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

Reference

  1. Martins KA, et al. Vaccine adjuvant uses of poly-IC and derivatives. Expert Rev Vaccines. 2015, 14(3): 447-59.

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