Poly I:C/poly-L-lysine: potent inducer of interferons in primates

Area of Science:

• Immunology
• Virology
• Biochemistry

Background:

• Polyriboinosinic:polyribocytidylic acid (poly I:C) is known to induce interferon.
• The development of stable and effective interferon inducers is crucial for antiviral therapies.
• Previous formulations of poly I:C have limitations in solubility and efficacy.

Purpose of the Study:

• To develop a soluble and potent interferon-inducing complex using poly I:C and poly-L-lysine.
• To evaluate the efficacy of this complex in inducing circulating interferon in non-human primates.
• To assess the durability of the interferon response and potential for hyporesponsiveness.

Main Methods:

• Preparation of a soluble poly I:C/poly-L-lysine complex with a specific lysine to nucleotide molar ratio (0.5).
• Testing complexes with varying poly-L-lysine molecular weights for interferon induction capacity in grivet monkeys.
• Administering the optimal complex repeatedly to grivet monkeys to assess sustained response and hyporesponsiveness.

Main Results:

• A soluble complex was formed at a lysine to nucleotide ratio of 0.5, stable up to 2.0 mg/ml.
• Poly-L-lysines with molecular weights of 10(4) daltons or greater significantly enhanced interferon induction (10- to 100-fold).
• The poly I:C/poly-L-lysine complex effectively induced high interferon titers in grivet monkeys, rhesus monkeys, chimpanzees, and marmosets, with sustained levels upon repeated administration and no long-term hyporesponsiveness.

Conclusions:

• The soluble poly I:C/poly-L-lysine complex is a potent inducer of circulating interferon in various primate species.
• Optimized complex formulation allows for sustained interferon production without inducing long-term hyporesponsiveness.
• This complex represents a promising candidate for therapeutic applications requiring interferon induction.