Background:

KIN1148, a small-molecule IRF3 agonist, is a novel influenza vaccine adjuvant found to enhance flu vaccine efficacy.

KIN1148 induces the dose-dependent nuclear translocation of IRF3 in PH5CH8 cells and specific activation of IRF3- responsive promoters. KIN1148 also elicits greater induction of endogenous IRF3-dependent ISG54 and OASL expression by PH5CH8 cells[1].

Prime-boost immunization of mice with a suboptimal dose of a monovalent pandemic influenza split virus H1N1 A/California/07/2009 vaccine plus KIN1148 protect against a lethal challenge with mouse-adapted influenza virus (A/California/04/2009) and induce an influenza virusspecific IL-10 and Th2 response by T cells derived from lung and lung-draining lymph nodes. Primeboost immunization with vaccine plus KIN1148, but not prime immunization alone, induce antibodies capable of inhibiting influenza virus hemagglutinin and neutralizing viral infectivity. Nevertheless, a single immunization with vaccine plus KIN1148 provide increased protection over vaccine alone and reduce viral load in the lungs after challenge[1].

[1]. Probst P, et al. A small-molecule IRF3 agonist functions as an influenza vaccine adjuvant by modulating the antiviral immune response. Vaccine. 2017 Apr 4;35(15):1964-1971.