Tick saliva molecules as potential immunomodulatory therapeutics

Ticks, infamous vectors of various pathogens, have evolved a unique strategy of saliva secretion during long-term feeding to suppress host defense mechanisms, including immune responses. This phenomenon may be a potential strategy to treat immune disorders and other diseases, offering a promising opportunity for exploiting parasite biology and parasite-derived molecules in drug discovery. This review examines the therapeutic potential of components in tick saliva, focusing on their mechanisms of action and clinical applications. It also discusses tick-derived immunomodulators, such as chemokine-binding proteins and complement inhibitors, that are currently attracting attention from the perspective of therapeutic drug development. Specifically, Ornithodoros moubata complement inhibitor (nomacopan), a C5 complement inhibitor contained in saliva from the soft tick O. moubata, has reached Phase III clinical trial status for hematopoietic stem cell transplantation-associated thrombotic microangiopathy and is considered an advanced research model in tick-derived drug development. The diverse and potent immunomodulatory properties of tick saliva molecules make them a potentially rich source for the identification and development of novel therapeutics, particularly for immune-mediated diseases.