immunogenic composition comprising an isolated polypeptide effective for inducing an immune response to liver stage Plasmodium falciparum in a mammalian subject, and a pharmaceutically acceptable carrier; use in the prevention, diagnosis, and treatment of malaria

Inventors

Duffy, Patrick • Krzych, Urszula • Heppner, JR., Donald G. • Malkov, Vladislav A. • WENDLER JASON P, null • Wendler, Jason W. • Bacik, Igor

Assignees

Drexel University • Seattle Biomedical Research Institute • Walter Reed Army Institute of Research • United States Department of the Army

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 an amino acid sequence selected from SEQ ID NOs:1-48 and immunogenic derivatives thereof, isolated nucleic acid molecules encoding these polypeptides, and compositions comprising one or more such polypeptides with a pharmaceutically acceptable carrier. The invention also includes methods for inducing an immune response against liver stage Plasmodium parasites, methods for treating malaria, genetically attenuated sporozoites lacking genes coding for liver stage polypeptides, expression vectors, host cells producing these polypeptides, antibodies specifically binding to these polypeptides or derivatives thereof, and diagnostic assays for detecting them.

Malaria poses a serious health risk by causing millions of deaths annually, with specific challenges related to infection at the liver stage, where sporozoites enter hepatocytes and mature before releasing merozoites that infect red blood cells. Existing vaccines and diagnostics have limited identification of liver stage-specific molecules. The problem addressed is the need for vaccines that protect against malaria infection and disease, as well as improved diagnostic markers for malaria, particularly targeting the liver stage of Plasmodium falciparum.

The invention overcomes these challenges by identifying liver stage-specific proteins and providing the corresponding isolated polypeptides and nucleic acids, which can be utilized in immunogenic compositions such as vaccines. These compositions induce immune responses effective against liver stage parasites. Additionally, the invention provides genetically attenuated parasites lacking liver stage genes to serve as potential live vaccines and includes methods to use antibodies specific to these proteins for diagnosis, treatment, and prevention of malaria.

Claims Coverage

The patent contains two independent claims focused on immunogenic compositions comprising isolated polypeptides effective for inducing immune responses against liver stage Plasmodium falciparum.

The claims focus on immunogenic compositions containing isolated polypeptides or domains thereof derived from SEQ ID NO:21 with at least 95% sequence identity, emphasizing their use to induce immune responses to liver stage Plasmodium falciparum in mammals.

Stated Advantages

Documented Applications