Plasmodium falciparum antigens and methods of use
Inventors
Sette, Alessandro • Doolan, Denise L. • Carucci, Daniel J. • Sidney, John • Southwood, Scott
Assignees
NAVY GOVERNMENT OF United States, Secretary of • NAVY United States, AS REPRESENTED BY SECRETARY OF • Epimmune Inc • US Department of Navy
Publication Number
US-8017745-B2
Publication Date
2011-09-13
Expiration Date
2023-12-08
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Abstract
The subject invention provides novel Plasmodium falciparum antigens and novel polynucleotides encoding these antigens. Also provided by the subject invention are methods of using these antigens and polynucleotides.
Core Innovation
The invention provides novel Plasmodium falciparum antigens and polynucleotides encoding these antigens. It further includes methods of using these antigens and polynucleotides, including isolated and purified polynucleotide sequences encoding polypeptides selected from SEQ ID NOs: 1 to 27 and their variants, fragments, and multi-epitope constructs. The invention also covers primers, probes, vectors, host cells, compositions, and methods of inducing immune responses using these materials.
The background identifies the problem of lacking means to efficiently analyze vast genomic sequencing data to identify appropriate antigen targets for vaccine development against P. falciparum. More than 5000 proteins expressed by the parasite pose a challenge, and current subunit vaccines based on few antigens elicit a narrow immune response, failing to provide optimal or broad protection. A vaccine targeting a large number of parasite-derived proteins through inclusion of their minimal CD8+ and CD4+ T cell epitopes in a multiepitope construct is desirable, but the specific antigens mediating whole organism-induced protection are largely unknown. Existing antigen identification approaches have limitations such as repetitive identification of dominant epitopes, underestimating complexity, and difficulties in analyzing large genomic datasets in the context of multiple HLA types.
Claims Coverage
The patent claims encompass multiple inventive features related to isolated polynucleotides, vectors, and transformed host cells encoding or comprising a specific Plasmodium falciparum polypeptide sequence and its HLA binding fragments, as well as methods for producing these polypeptides.
Isolated polynucleotide encoding a specific Plasmodium falciparum polypeptide or HLA binding fragments
An isolated or purified polynucleotide encoding a polypeptide comprising SEQ ID NO: 1, or encoding specific Human Leukocyte Antigen (HLA) binding fragments comprising amino acid sequences selected from SEQ ID NOs: 28 to 37, or complementary sequences to them.
Vector comprising a promoter operably linked to the polynucleotide
Vectors comprising a promoter operably linked to a polynucleotide encoding the polypeptide comprising SEQ ID NO: 1, encoding the specific HLA binding fragments, or complementary sequences thereto.
Isolated transformed host cell comprising the polynucleotide or vector
Isolated transformed host cells containing the polynucleotide encoding SEQ ID NO: 1, the HLA binding fragments, or complementary sequences, including those cells transformed with the claimed vectors.
Method of making the polypeptide by culturing transformed host cells
Methods for producing the polypeptide by culturing the isolated transformed host cells under conditions allowing polypeptide expression.
The claims cover the isolated nucleic acids encoding the novel malaria antigen SEQ ID NO: 1 and its HLA binding fragments, vectors designed for expression of these nucleic acids, transformed host cells containing these vectors or nucleic acids, and methods of producing the encoded polypeptides, emphasizing specific peptide sequences recognized by the immune system.
Stated Advantages
Provides novel Plasmodium falciparum antigens with broad immune reactivity exceeding known antigens, facilitating improved vaccine targets.
Enables efficient identification of immunogenic epitopes across multiple HLA types from genomic data, overcoming limitations of previous antigen discovery methods.
Supports development of multiepitope constructs for inducing protective immune responses mimicking whole organism immunity.
Facilitates diverse therapeutic and diagnostic applications including nucleic acid-based detection assays and immunoassays.
Documented Applications
Uses in therapeutic and diagnostic applications for malaria, including composition administration for immune response induction against P. falciparum.
Diagnostic assays such as Western blots, standard immunoassays, ELISAs, and immunochromatographic assays employing identified antigens or peptides.
DNA or RNA-based methods to detect P. falciparum in biological samples via hybridization, PCR, RT-PCR, and DNA chip microarray technologies.
Vaccination approaches involving polynucleotide vaccines and polypeptide antigens, including prime-boost regimens with viral vectors and adjuvants.
Production of isolated polypeptides and antibodies for research, diagnostic, or therapeutic use.
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