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AssigneeSeattle Children's Hospital
InventorsAshley M. Vaughan, Stefan H. I. Kappe, Dorender A. Dankwa
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The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.
A live Plasmodium organism that is genetically modified to disrupt PlasMei2 gene function, wherein a functional PlasMei2 gene comprises a nucleic acid sequence with at least 90% identity to the sequence set forth in SEQ ID NO:9, wherein the Plasmodium organism further comprises at least one transgene encoding an antigen, and wherein the Plasmodium organism infects a human host.
A method for stimulating an immune response against an antigen in a host subject, comprising administering to the host subject a live Plasmodium organism that comprises at least one transgene encoding the antigen and is further genetically modified to disrupt PlasMei2 gene function, wherein a functional PlasMei2 gene comprises a nucleic acid sequence with at least 90% identity to the sequence set forth in SEQ ID NO:9, and wherein the Plasmodium organism infects a human host and the antigen encoded by the transgene is expressed by the Plasmodium organism in the host and stimulates a host immune response.
Dependencies are inferred from the claim text.