Plasmodium liver stage antigens
Inventors
Duffy, Patrick • Kappe, Stefan H. I. • Krzych, Urszula • Heppner, Donald G. • Bergman, Lawrence W. • Malkov, Vladislav A. • Tarun, Alice • Wendler, Jason P. • Bacik, Igor
Assignees
Seattle Biomedical Research Institute • Philadelphia Health and Education Corp • Walter Reed Army Institute of Research
Publication Number
US-8318183-B2
Publication Date
2012-11-27
Expiration Date
2026-09-29
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Abstract
The invention provides isolated liver stage Plasmodium polypeptides comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:1-48 and immunogenic derivatives thereof. The invention also provides isolated nucleic acid molecules encoding the liver stage Plasmodium polypeptides of the invention, compositions comprising one or more liver stage Plasmodium polypeptides of the invention, methods for inducing an immune response against the liver stage Plasmodium polypeptides, and methods for treating and diagnosing liver stage malaria.
Core Innovation
The invention provides isolated liver stage Plasmodium polypeptides comprising amino acid sequences selected from SEQ ID NOs:1-48 and immunogenic derivatives thereof, isolated nucleic acid molecules encoding these polypeptides, compositions containing one or more of these polypeptides, methods for inducing immune responses against liver stage Plasmodium parasites, and methods for treating and diagnosing liver stage malaria. It also includes genetically attenuated sporozoites lacking liver stage genes, expression vectors encoding liver stage polypeptides, host cells containing such vectors, antibodies specific to the polypeptides, and diagnostic assays for detection.
Malaria poses a major global health problem causing millions of deaths annually and impedes social and economic development. Infection begins with injection of sporozoites by mosquitoes, which invade hepatocytes and develop into liver stages releasing merozoites that infect red blood cells. Liver stages express unique proteins important as targets for sterile protective immunity, but only a few liver stage-specific molecules have been identified. The liver stage is the primary target for protective immune responses in vaccine models. There is a need for malaria vaccines that protect against infection and disease and for diagnostic markers for malaria, which this invention addresses.
Claims Coverage
The patent includes multiple claims with one independent claim focused on a specific isolated polypeptide and immunogenic compositions thereof. The inventive features revolve around isolated polypeptides with high sequence identity to a defined liver stage Plasmodium polypeptide and related immunogenic compositions.
Isolated polypeptide with high amino acid sequence identity to a liver stage protein
An isolated polypeptide comprising an amino acid sequence with at least 95% identity to SEQ ID NO:20, a liver stage Plasmodium falciparum protein.
Immunogenic composition comprising isolated polypeptide
An immunogenic composition containing an isolated polypeptide with at least 95% amino acid sequence identity to SEQ ID NO:20 and a pharmaceutically acceptable carrier.
Immunogenic composition with polypeptide domain
An immunogenic composition comprising an isolated polypeptide with amino acid sequence corresponding to amino acids 151-326 of SEQ ID NO:20 and a pharmaceutically acceptable carrier.
The claims focus on isolated liver stage Plasmodium polypeptides highly similar to SEQ ID NO:20 and compositions thereof for immunogenic use, highlighting specific polypeptide domains useful in vaccine formulations.
Stated Advantages
The liver stage Plasmodium proteins are preferentially targeted by immune responses associated with protection from Plasmodium infection.
Liver stage proteins or derivatives are antigenic targets of T cell immunity correlating with protection.
Recombinant or synthetic polypeptides and immunogenic derivatives can be produced for vaccines and diagnostic uses.
Documented Applications
Use of liver stage Plasmodium polypeptides for vaccine compositions inducing immune responses against liver stage malaria infections.
Use of immunogenic compositions to treat or prevent malaria in mammalian subjects.
Development of genetically attenuated Plasmodium sporozoites lacking liver stage genes for use as live vaccines.
Diagnostic methods and assays using liver stage Plasmodium polypeptides or antibodies thereto to detect malaria infection.
Preparation of DNA or viral vaccines encoding liver stage Plasmodium polypeptides.
Screening and monitoring immune status of subjects vaccinated against P. falciparum infection.
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