The Development of an Aspergillus Fumigatus Vaccine for Protection Against Pulmonary Aspergillosis in Mammals

Introduction: Aspergillus fumigatus, the most common cause of pulmonary aspergillosis, affects immunosuppressed people with a survival rate of 58% despite antifungal treatment. The present studies were done to compare the efficacy of vaccinating mice with a sublethal dose of A. fumigatus versus (vs) a liposomal vaccine (LV) containing A. fumigatus proteins Aspf3, Aspf9, and Hemolysin (He), and the adjuvant monophosphoryl Lipid A(MPL). Methods and Results: Mice were given A. fumigatus intranasally (i.n.)(3.2x10^6 spores/mouse) or buffer on d0, and d21 challenged i.n. with A. fumigatus (1.5x10^7 spores/mouse). Survival was only 29% for vaccinated mice, with BAL and lung fungal burdens similar to buffer mice (Lungs, 3.3x10^5CFU/g vs 1.2x10^5CFU/g; BAL, 2.9x10^3CFU/mL vs 2.2x10^3CFU/mL) and elevated anti-Aspergillus antibody titers for vaccinated vs buffer mice. Thus, anti-Aspergillus antibodies did not confer protection. Other mouse groups were vaccinated subcutaneously d0, and i.n. d21 and d49 with Asp3, Asp9, and He liposomes at 5, 10, or 25ug for each protein/dose or buffer and challenged i.n. d63 with 8.10x10ex6spores/mouse. Survival was highest with 5ug/dose vs buffer mice( 70% vs 30%, respectively) with average lung CFU of 1.0x10^5/g vs 6.2x10^5/g (p