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Publication Number
US-10195260-B2
Publication Date
2019-02-05
Expiration Date
Abstract
The present invention provides polypeptides useful as antigens expressed at the pre-erythrocytic stage of the malaria parasite. The antigens can be utilized to induce an immune response and sterile protection against malaria in a mammal by administering the antigens in vaccine formulations or expressing the antigens in DNA or other recombinant protein expression systems delivered as a vaccine formulation.
Core Innovation
The document describes malaria pre-erythrocytic antigen polypeptides, including Plasmodium yoelii E140 (PY06306) and orthologs such as Plasmodium falciparum E140 (Pf E140; PFA0205w) and Plasmodium vivax E140 (PvE140; PVX_081555), for inducing immune responses and for providing sterile protection against malaria. It frames pre-erythrocytic targeting as a strategy to act during malaria infection prior to erythrocyte stages.
The document further provides immunogenic compositions including recombinant polypeptides comprising SEQ ID NO:3 (E140) and pharmaceutically acceptable carriers and adjuvants. It additionally describes combining E140-based polypeptides with one or more additional recombinant polypeptides selected from specified SEQ ID sequences (SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9) or recombinant polypeptides containing at least 10 contiguous amino acids from those sequences with specified sequence identity criteria.
Mechanistic and performance support is described for E140-containing regimens in mouse sporozoite challenge studies, reporting high levels of sterile protection and associated outcomes such as delayed parasitemia and correlating antibody titers. The document reports that sterile protection persists despite CD4 and CD8 T-cell depletion, that sera transfer can delay infection, and that immune reactivation is supported by CD8 T-cell epitope recall, with additional evidence that Pf E140 peptide pools can induce T-cell responses in radiation-attenuated sporozoite subject contexts.
Claims Coverage
The independent claims define an immunogenic composition centered on a recombinant E140 polypeptide (SEQ ID NO:3) formulated with a pharmaceutically acceptable carrier and an adjuvant, with sequence constraints and, for one independent claim, additional specified recombinant polypeptides. The inventive aspects are captured by two independent claim structures, together requiring specific recombinant polypeptide identity/contiguity criteria and (for one claim) defined sets of additional recombinant polypeptides.
E140 recombinant polypeptide composition with carrier and adjuvant
An immunogenic composition comprising a recombinant polypeptide wherein the recombinant polypeptide comprises SEQ ID NO:3, or a recombinant polypeptide that comprises at least 10 contiguous amino acids of SEQ ID NO:3 and has at least 85% sequence identity with SEQ ID NO:3; a pharmaceutically acceptable carrier; and an adjuvant.
E140 recombinant polypeptide plus additional specified recombinant polypeptides
An immunogenic composition comprising a recombinant polypeptide wherein the recombinant polypeptide comprises SEQ ID NO:3, or a recombinant polypeptide that comprises at least 10 contiguous amino acids of SEQ ID NO:3 and has at least 85% sequence identity with SEQ ID NO:3; a pharmaceutically acceptable carrier; and an adjuvant; further comprising one or more additional recombinant polypeptides wherein the one or more additional recombinant polypeptides comprise an amino acid sequence selected from SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or a recombinant polypeptide that comprises at least 10 contiguous amino acids of SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9 and has at least 85% sequence identity with one of SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.
Across the independent claims, coverage is directed to immunogenic compositions built around a recombinant polypeptide comprising SEQ ID NO:3 (E140) with defined contiguous-amino-acid and sequence-identity thresholds, formulated with a pharmaceutically acceptable carrier and an adjuvant. One independent claim additionally requires one or more additional recombinant polypeptides selected from the enumerated SEQ ID NO:6/7/8/9 options with corresponding sequence criteria.
Stated Advantages
Provides sterile protection against malaria.
Induces immune responses.
Documented Applications
Pre-erythrocytic targeting for malaria, including sterile protection in mouse sporozoite challenge studies.
Use of E140-containing immunogenic compositions in radiation-attenuated sporozoite subject contexts to support T-cell responses.
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