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Publication Number
US-11793868-B2
Publication Date
2023-10-24
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 disclosure relates to malaria vaccine candidates based on malaria pre-erythrocytic antigens. It describes malaria pre-erythrocytic antigens including E140 and orthologs, such as P. falciparum PfE140 and P. vivax PvE140, as vaccine antigens expressed at sporozoite and liver stages. The immunogenic compositions are formulated to induce cellular and humoral immunity, including antibodies and T-cell responses, directed to these antigens at the pre-erythrocytic stage.
The problem addressed is the lack of an effective malaria vaccine, including shortcomings of prior malaria vaccine approaches described in the background. The disclosure supports that administering immunogenic compositions containing recombinant Plasmodium E140 polypeptides, including SEQ ID NO: 3, can provide sterile protection against pre-erythrocytic infection in a mouse sporozoite challenge model. The evidence described includes protection metrics and immunologic findings such as cross-stage antibodies and immunogenicity.
The disclosure further supports use of immunogenic compositions comprising recombinant polypeptides together with pharmaceutical acceptable carriers and adjuvants. It includes delivery and formulation approaches using DNA, recombinant protein, and vector delivery, and it also describes combination formulations and additional recombinant polypeptides. The antigen expression and localization in parasites and immune response features are described, including T-cell responses in mice and human T-cell responses.
Claims Coverage
The partial claim set includes two independent claims. Each independent claim centers on administering an immunogenic composition containing a recombinant Plasmodium E140 polypeptide comprising the amino acid sequence of SEQ ID NO: 3, with a pharmaceutical acceptable carrier and an adjuvant, and one independent claim additionally recites optional additional recombinant polypeptides selected from specified sequences.
Recombinant Plasmodium E140 antigen immunogenic composition with adjuvant
Administering to a subject an immunogenic composition comprising a recombinant Plasmodium E140 polypeptide comprising the amino acid sequence of SEQ ID NO: 3, a pharmaceutical acceptable carrier, and an adjuvant, wherein the recombinant Plasmodium E140 polypeptide is an E140 antigen of a Plasmodium falciparum strain.
Multi-polypeptide E140 immunogenic composition with additional recombinant polypeptides
Administering to a subject an immunogenic composition comprising a recombinant Plasmodium E140 polypeptide comprising the amino acid sequence of SEQ ID NO: 3, a pharmaceutical acceptable carrier, and an adjuvant, wherein the immunogenic composition further comprises one or more additional recombinant polypeptides comprising an amino acid sequence selected from SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, or a recombinant polypeptide comprising 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 having 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, the coverage is directed to inducing an immune response through administration of immunogenic compositions containing a recombinant Plasmodium E140 polypeptide defined by SEQ ID NO: 3, together with a pharmaceutical acceptable carrier and an adjuvant. The broader independent claim also optionally includes additional recombinant polypeptides selected from specified SEQ ID NOs or contiguous segments with specified sequence identity.
Stated Advantages
Induces an immune response in a subject.
Provides sterile protection against pre-erythrocytic infection in a mouse sporozoite challenge model [procedural detail omitted for safety].
Provides cross-stage antibodies and humoral and cellular immune responses, including T-cell responses, as described in the disclosure.
Documented Applications
Malaria vaccination targeting pre-erythrocytic stages (sporozoite and liver stages) using E140 antigens to induce cellular and humoral immunity and sterile protection.
Inducing an immune response in a subject via administration of immunogenic compositions comprising recombinant Plasmodium E140 polypeptides with a pharmaceutical acceptable carrier and an adjuvant.
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