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US 10,092,632 B2Granted
Vaccination against Cryptococcus
AssigneeWashington University
InventorsJennifer Lodge, Woei Lam, Rajendra Upadhya
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AssigneeWashington University
InventorsJennifer Lodge, Woei Lam, Rajendra Upadhya
Estimating the term…
Vaccines and methods of inoculation for conferring immunity to Cryptococcus infection are disclosed. Strains of Cryptococcus fungi, including Cryptococcus neoformans and Cryptococcus gattii, can be administered to a human or animal subject via inhalation. Cryptococcus fungi that can be used to confer immunity can comprise one or more mutations in genes that contribute to chitosan production, such as genes encoding a chitin deacetylase (cda), a chitin synthase (chs) and/or a regulator of chitin synthase (csr). Inhalation administration of heat-killed Cryptococcus harboring deletions in cda1, cda2 and cda3 genes can confer immunity. In a murine model system, inhalation administration of Cryptococcus neoformans harboring deletions in cda1, cda2 and cda3 genes conferred immunity against subsequent exposure to wild type Cryptococcus neoformans in 100% of test animals. Inhalation administration of heat-killed Cryptococcus grown under conditions leading to reduced chitosan production can also confer immunity.
A method of inducing immunity against a Cryptococcus fungus infection wherein the Cryptococcus is selected from the group consisting of Cryptocoecus neoformans and Cryptococcus gattii, comprising administering to a subject by inhalation an immunity-inducing amount of a composition comprising a Cryptococcus fungus deficient for chitosan, wherein the Cryptococcus fungus deficient for chitosan is selected from the group consisting of a Cryptococcus neoformans fungus deficient for chitosan and a Cryptococcus gattii fungus deficient for chitosan, and wherein the Cryptococcus fungus deficient for chitosan comprises no more than 60% chitosan level compared to wild type grown on yeast extract peptone dextrose (YPD) and wherein the Cryptococcus fungus deficient for chitosan is a heat-inactivated cdaIΔcda2Δcda3Δ Cryptococcus fungus deficient for chitosan.
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