PROJECT SUMMARY Influenza is an acute respiratory virus infection that poses endemic, zoonotic and pandemic threats to human health with significant morbidity and mortality. Natural killer (NK) cells and virus-specific CD8 T cells are key effector cells in launching effective immune responses against influenza virus infection. ImmulinaTM, a high molecule-weight fraction of Spirulina extract, contains Braun-type lipoproteins that trigger Toll-like receptor 2 (TLR2)-mediated NFκB activation in human monocytes and mouse macrophages. Our recent preliminary data show that daily treatment of a liquid formulation of Immulina caused notable expansion of circulating NK population in mice. Building upon our substantial experience in drug delivery, pharmacodynamics and immunology, we propose to develop an optimized liquid formulation of Immulina, evaluate its protective effect against influenza virus infection, and elucidate the mechanism of action in vitro and in vivo. The specific aims of the proposal are: (1) develop an optimized liquid formulation for Immulina; (2) evaluate the pharmacodynamics of Immulina and identify in vivo biomarker(s); (3) investigate the molecular mechanism on the immune enhancement by Immulina. The successful completion of this project will result in the development of an improved formulation of Immulina and the identification of in vivo biomarkers for Immulina treatment.