Abstract: The present invention is directed to a method for removing cytokines and/or pathogens from blood or blood serum (blood) by contacting the blood with a solid, essentially non microporous substrate which has been surface treated with heparin, heparan sulfate and/or other molecules or chemical groups (the adsorbent media or media) having a binding affinity for the cytokine or pathogen(s) to be removed (the adsorbates), and wherein the size of the interstitial channels within said media is balanced with the amount of media surface area and the surface concentration of binding sites on the media in order to provide adequate adsorptive capacity while also allowing relatively high flow rates of blood through the adsorbent media.

Abstract: The present invention relates to a novel lipoprotein particle, methods for preparing and purifying the same, its use in medicine, particularly in the prevention of malarial infections, compositions/vaccines containing the particle or antibodies against the protein particle such as monoclonal or polyclonal antibodies and use of the same, particularly in therapy. In particular it relates to an immunogenic protein particle comprising the following monomers: a. a fusion protein comprising sequences derived from a CS protein of P. vivax and the S antigen of Hepatitis B (CSV-S), and b. a fusion protein comprising sequences derived from CS protein of P. falciparum and S antigen of Hepatitis B (RTS), and c. optionally the S antigen derived from Hepatitis B.

Abstract: The present invention provides a novel transfer vector and a recombinant baculovirus; methods for the production thereof; pharmaceuticals containing the recombinant baculovirus as an active ingredient, which are useful as preventive or therapeutic drugs for infectious diseases such as malaria and influenza; and methods for preventing and treating infectious diseases such as malaria and influenza. More specifically, the invention provides a recombinant transfer vector capable of expressing a foreign gene fused to a virus gene under the control of a dual promoter; a recombinant baculovirus; methods for the production thereof; pharmaceuticals containing the recombinant baculovirus as an active ingredient; and methods for preventing and treating infectious diseases such as malaria and influenza comprising administrating the recombinant baculovirus to patients.

Abstract: The present invention provides a vaccine for preventing and/or treating Plasmodium falciparum infections, which comprises a polypeptide set forth in SEQ ID NO: 1 or represented by formula (1), and an adjuvant. X1-A-B-X2-Y-X3-(Y)n-X4-(Y)n-X5??(1) (In the formula, X1 represents the 1st to 7th amino acid residues in a polypeptide set forth in SEQ ID NO: 1; X2 represents the 73th to 177th amino acid residues; X3 represents the 178th to 258th amino acid residues; X4 represents the 259th to 289th amino acid residues; X5 represents the 290th to 334th amino acid residues; A represents an 8-mer repeat sequence contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum; B represents a sequence of a serine-rich region contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum; Y represents any one selected from A-A, A-B, and B; and n is an integer of 0 or 1).

Abstract: The present invention provides anti-Plasmodium immunogenic compositions comprising EVP1 (PFD0495c) or an antigenic portion thereof, as well as methods of immunizing against malaria employing these compositions. In other embodiments, the present invention provides methods of identifying Plasmodium infection employing agents that bind to EVP1 or an antibody generated thereto.

Abstract: The present invention relates to a novel lipoprotein particle, methods for preparing and purifying the same, its use in medicine, particularly in the prevention of malarial infections, compositions/vaccines containing the particle or antibodies against the protein particle such as monoclonal or polyclonal antibodies and use of the same, particularly in therapy. Furthermore, particles with the specific ratio can be prepared by employing yeast, Saccharomyces cerevisiae or Pichia pastoris. In particular it relates to an immunogenic protein particle comprising the following monomers: a. a fusion protein comprising sequences derived from a CS protein of P. vivax and the S antigen of Hepatitis B (CSV-S), and b. S antigen derived from Hepatitis B virus, and characterized in that the ratio of S to CSV-S is in the range 0.1 to 1. Suitably, the ratio of S to CSV-S is in the range 0.19 to 0.30 or 0.68 to 0.80.

Abstract: Conjugates of ookinete surface protein Pfs25 are provided that are efficacious as vaccines against Plasmodium falciparum, the most severe form of malaria. Conjugates of ookinete surface protein Pvs25 for use as a vaccine against Plasmodium vivax are also provided. Methods for preparing the conjugates, which comprise the ookinete surface protein bound onto itself or onto another protein by a linking group, are also provided.

Abstract: The present invention provides a vaccine for preventing and/or treating Plasmodium falciparum infections, which comprises a polypeptide set forth in SEQ ID NO: 1 or represented by formula (1), and an adjuvant. X1-A-B-X2-Y-X3-(Y)n-X4-(Y)n-X5??(1) (In the formula, X1 represents the 1st to 7th amino acid residues in a polypeptide set forth in SEQ ID NO: 1; X2 represents the 73th to 177th amino acid residues; X3 represents the 178th to 258th amino acid residues; X4 represents the 259th to 289th amino acid residues; X5 represents the 290th to 334th amino acid residues; A represents an 8-mer repeat sequence contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum; B represents a sequence of a serine-rich region contained in a 47-kd region of SERA polypeptide of Plasmodium falciparum; Y represents any one selected from A-A, A-B, and B; and n is an integer of 0 or 1.

Abstract: The present invention belongs to the field of vaccines for the prevention and prophylaxis against malaria, more specifically it relates to exosomes isolated from reticulocytes infected with Plasmodium sp., to methods for obtaining them and to the use thereof for the prevention and prophylaxis against malaria as well as to its use for the discovery and identification of novel Plasmodium antigens. The invention also refers to artificial exosomes comprising Plasmodium sp. antigens. Finally, the invention refers to specific antigens discovered by means of the exosomes obtained from reticulocytes infected with Plasmodium sp.

Abstract: The disclosure provides compositions that are useful for eliciting a strain-transcending immune response in an animal or human directed against the blood-stage of the malarial parasite Plasmodium vivax. The compositions are based on the ligand domain of Plasmodium vivax Duffy binding protein (PvDBPII). Polar charged polymorphic residues within the dominant strain-specific B-cell epitope were mutated to uncharged residues (e.g. serine, alanine and threonine). This DEKnull variant of PvDBPII produced in bacteria can be purified and refolded in vitro to mimic conformation and erythrocyte binding function of native DBPII. Immunogenicity of DEKnull was confirmed by administration to mice. Compared to the naturally-occurring, strain variant DBPII, DEKnull elicits antibodies that are more broadly reactive with different strain variants of DBPII and enhances production of functional inhibitory antibodies to the shared protective epitopes of native DBPII.

Abstract: The invention provides adenoviral vectors comprising an adenoviral genome comprising heterologous antigen-encoding nucleic acid sequences, such as Plasmodium nucleic acid sequences, operably linked to promoters. The invention further provides a method of inducing an immune response against malaria in a mammal comprising administering the adenoviral vectors to the mammal.

Abstract: Malaria vaccines based on polyepitope constructs that elicit cell-mediated immunity against a broad spectrum of malaria parasites and which cover the majority of HLA alleles are provided. Epitopes in the polyepitope constructs are from regions of the Plasmodium falciparum circumsporozoite protein (CSP) known to contain CD4 and CD8 T cell epitopes, and include both epitopes from highly variable and highly conserved regions of CSP.

Abstract: The disclosure provides novel antigens involved in gestational malaria, and more particularly to polynucleotide and polypeptide sequences, conjugates, cloning vectors including the sequences for the preparation of immunogenic compositions and vaccines, antibodies, and to their for treating gestational malaria. Diagnostic methods and kits are described.

Abstract: The present invention relates generally to a method of eliciting or otherwise inducing an effective immune response to a micro-organism and compositions for use therein. More particularly, the present invention relates to a method of inducing an immune response to a parasite utilising an immunogenic composition comprising a glycosylphosphatidylinositol (referred to herein as “GPI”) inositolglycan domain or its derivatives. Even more particularly, the present invention contemplates an immunogenic composition comprising the Plasmodium falciparum GPI inositolglycan domain or its derivatives. The present invention is useful, inter alia, as a prophylactic and/or therapeutic treatment for disease conditions such as, for example, infection by parasites and in particular infection by Plasmodium species.

Abstract: The present invention provides anti-Plasmodium immunogenic compositions comprising EVP1 (PFD0495c) or an antigenic portion thereof, as well as methods of immunizing against malaria employing these compositions. In other embodiments, the present invention provides methods of identifying Plasmodium infection employing agents that bind to EVP1 or an antibody generated thereto.

Abstract: The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.

Abstract: The present invention provides a one phase, aqueous vaccine composition for immunizing an animal against infection by Mycoplasma hyopneumoniae, comprising: an immunizing amount of a Mycoplasma hyopneumoniae bacterin, an acrylic acid polymer in the concentration range between 0.8 and 1.2 mg/ml, and a pharmaceutically acceptable carrier, and substantially no oil. It is especially useful for immunizing a pig against infection by Mycoplasma hyopneumoniae for at least 20 weeks after a single administration, which effective immunity is reached within 4 weeks after vaccination.

Abstract: Conjugates of ookinete surface protein Pfs25 are provided that are efficacious as vaccines against Plasmodium falciparum, the most severe form of malaria. Conjugates of ookinete surface protein Pvs25 for use as a vaccine against Plasmodium vivax are also provided. Methods for preparing the conjugates, which comprise the ookinete surface protein bound onto itself or onto another protein by a linking group, are also provided.

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.

Abstract: The present invention relates to live attenuated bacteria of the species Pasteurella multocida, to live attenuated vaccines comprising such live attenuated bacteria, to the use of such bacteria for the manufacture of such vaccines, to methods for the preparation of such vaccines and to diagnostic tests for the detection of such bacteria.

Abstract: In this application is the expression and purification of a recombinant Plasmodium falciparum (3D7) MSP-142. The method of the present invention produces a highly purified protein which retains folding and disulfide bridging of the native molecule. The recombinant MSP-142 is useful as a diagnostic reagent, for use in antibody production, and as a vaccine.

Abstract: The subject invention relates to nucleic acid sequences and amino acid sequences encoded thereby, derived from the Merozoite Surface Protein (MSP1) gene of the Plasmodium species P. malariae and P. ovale. Such genes and proteins have many beneficial diagnostic as well as therapeutic uses.

Abstract: The present invention provides isolated polynucleotides, polypeptides, antibodies and/or vaccines for the prevention and/or treatment of malaria caused by Plasmodium falciparum and/or Plasmodium vivax. In particular, the polypeptide fragments are derived from the binding domain of the reticulocyte binding proteins of Plasmodium falciparum and/or Plasmodium vivax. The present invention also provides recombinant vaccines and their use in the prevention and/or treatment of malaria.

Abstract: The present inventors succeeded in isolating GWT1 (PfGWT1), which is one of the enzymes involved in GPI biosynthesis in the malaria parasite P. falciparum. In addition, the inventors revealed that degenerate mutant DNAs, with a lower AT content than the DNA encoding the PfGWT1 protein, can complement the phenotype of GWT1-deficient yeast. Based on the findings, the present invention provides the GWT1 protein of malaria parasites and the use of the protein in methods of screening for antimalarial drugs. The present invention also provides degenerate mutant DNAs encoding proteins involved in GPI biosynthesis, and which have a lower AT content than the original DNAs. The present invention also provides methods of screening for antimalarial drugs which use the degenerate mutant DNAs.

Abstract: In this application is described the expression and purification of a recombinant Plasmodium falciparum (FVO) MSP-142. The method of the present invention produces a highly purified protein that retains folding and disulfide bridging of the native molecule. The recombinant MSP-142 is useful as a diagnostic reagent, for use in antibody production, and as a vaccine.

Abstract: The present invention relates to an immunogenic agent comprising a low dose of an antigenic component from one or more pathogens and an agent capable of increasing an amount of IL-12 in animal, and use thereof for reducing infection or improving recovery from an infection from the pathogen. The immunogenic agent preferably comprises CpG nucleic acid, IL-12 protein and/or IL-12 nucleic acid. The pathogen is preferably an intracellular pathogen comprising one or more species and strains, such as Plasmodium spp. The invention also relates to a pharmaceutical composition comprising the immunogenic agent. The pharmaceutical composition is preferably an immunotherapeutic composition. The immunotherapeutic composition, is preferably a vaccine capable of providing protection against or treating Plasmodium spp infection, the causative agent of malaria in humans.

Abstract: The present invention relates to a malaria vaccine for administration to a host comprising an attenuated malarial parasite with a gene which has been rendered non-functional, wherein the gene, when present in naturally occurring form, encodes a protein necessary for continued in vivo survival and proliferation of the parasite and for infection of host red blood cells. The invention further relates to a malaria vaccine in which a gene that encodes a nutrient transporter protein has been rendered non-functional.

Abstract: The present invention relates to a method of inducing an immune response to a parasite utilizing an immunogenic composition comprising a glycosylphosphatidylinositol (“GPI”) inositolglycan domain or its derivative or equivalent. The present invention is useful as a prophylactic and/or therapeutic treatment for microorganism infections of mammals such as parasite infections and particularly infection by Plasmodium species. The invention also provides a method of monitoring, or qualitatively or quantitatively assessing an immune response to a microorganism such as a parasite.

Abstract: The subject invention relates to nucleic acid sequences and amino acid sequences encoded thereby, derived from the Merozoite Surface Protein (MSP1) gene of the Plasmodium species P. malariae and P. ovale. Such genes and proteins have many beneficial diagnostic as well as therapeutic uses.

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.

Abstract: The present inventors succeeded in isolating GWT1 (PfGWT1), which is one of the enzymes involved in GPI biosynthesis in the malaria parasite P. falciparum. In addition, the inventors revealed that degenerate mutant DNAs, with a lower AT content than the DNA encoding the PfGWT1 protein, can complement the phenotype of GWT1-deficient yeast. Based on the findings, the present invention provides the GWT1 protein of malaria parasites and the use of the protein in methods of screening for antimalarial drugs. The present invention also provides degenerate mutant DNAs encoding proteins involved in GPI biosynthesis, and which have a lower AT content than the original DNAs. The present invention also provides methods of screening for antimalarial drugs which use the degenerate mutant DNAs.

Abstract: The present invention provides a polypeptide SE36 derived from the N-terminal domain (47 kd) of SERA (serine-repeat antigen) produced by malaria parasite, Plasmodium falciparum, at the erythrocyte stage, a process for purifying said polypeptide, and a malaria vaccine and diagnostic agent using as an active component said purified antigen obtained therefrom. SE36 can be produced in Escherichia coli on a large scale by deleting all or part of polymerized serines of the 47 kd serine-repeat region, whereby high purification is permitted. The human IgG3 antibodies specifically binding to SE36 prevents highly effectively growth of the protozoa in the red blood cells to inhibit fever and cerebral malaria, and further prevent the death.

Abstract: The invention relates to polypeptide carrier proteins that comprise at least five CD4+ T cell epitopes, for conjugation to capsular polysaccharides. The carrier proteins are useful as components of vaccines that can elicit a T-cell dependent immune response. These vaccines are particularly useful to confer protection against infection from encapsulated bacteria in infants between the ages of 3 months and about 2 years.

Abstract: The present invention relates to a purified polypeptide comprising or consisting of a C-terminus MSP1 antigen from Plasmodium falciparum carrying a Glycosyl-phosphatidyl-inositol group (GPI), an immunogenic composition and a vaccine against a Plasmodium infection comprising said purified polypeptide.

Abstract: Described in this application is a synthetic P. vivax circumsporozoite protein useful as a diagnostic reagent, for antibody production, and as a vaccine protective against infection with any strain of P. vivax.

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.

Abstract: The invention provides methods for inducing an immune response in a vertebrate host against a protozoan parasite, comprising administering to the host a live protozoan parasite that is genetically engineered to disrupt a stage-specific gene function that is required by the protozoan parasite to establish a secondary infection in the vertebrate host. Representative protozoan parasites belong to the phyla Apicomplexa and Kinetoplastida. The vertebrate host may be a mammal or a bird.

Abstract: In this application is described the expression and purification of a recombinant Plasmodium falciparum (FVO) MSP-142. The method of the present invention produces a highly purified protein that retains folding and disulfide bridging of the native molecule. The recombinant MSP-142 is useful as a diagnostic reagent, for use in antibody production, and as a vaccine.

Abstract: In this application is the expression and purification of a recombinant Plasmodium falciparum (3D7) MSP-142. The method of the present invention produces a highly purified protein which retains folding and disulfide bridging of the native molecule. The recombinant MSP-142 is useful as a diagnostic reagent, for use in antibody production, and as a vaccine.

Abstract: The present invention relates generally to a method of eliciting or otherwise inducing an effective immune response to a micro-organism and compositions for use therein. More particularly, the present invention relates to a method of inducing an immune response to a parasite utilising an immunogenic composition comprising a glycosylphosphatidylinositol (referred to herein as “GPI”) inositolglycan domain or its derivatives. Even more particularly, the present invention contemplates an immunogenic composition comprising the Plasmodium falciparum GPI inositolglycan domain or its derivatives. The present invention is useful, inter alia, as a prophylactic and/or therapeutic treatment for disease conditions such as, for example, infection by parasites and in particular infection by Plasmodium species.

Abstract: Methods for improving binding of a proteinaceous substance to cell-wall material of a Gram-positive bacterium are disclosed. The proteinaceous substance includes an AcmA cell-wall binding domain, homolog or functional derivative thereof. The method includes treating the cell-wall material with a solution capable of removing a cell-wall component such as a protein, lipoteichoic acid or carbohydrate from the cell-wall material and contacting the proteinaceous substance with the cell-wall material.

Abstract: The invention concerns novel Plasmodium falciparum antigens and their vaccine and diagnostic applications. More particularly, the invention concerns immunogenic polynucleotide and polypeptide molecules, compositions comprising them, and methods for diagnosis and vaccination of malaria.

Abstract: Antigenic and immunogenic determinants of Merozoite surface protein 3 (MSP3). Antigenicity and functional assays identified a 68-amino acid conserved domain of MSP3 as a target of biologically active antibodies. A peptide comprising amino acid residues 184-251 of SEQ ID NO: 2, may also be employed as may peptides consisting of different combinations of the MSP3 a, b, c, d, e and f peptides. Particular non-overlapping or overlapping segments of MSP3 a, b, c, d, e and f peptides may also be used. The various overlapping segments and nonoverlapping segments among the different MSP3 peptides are shown in FIG. 6. MSP3 determinants include targets of antibody-dependent cellular inhibition (ADCI) which is a protective mechanism against Plasmodium falciparum malaria. Six overlapping peptides were derived from the C-terminal end of the MSP3 polypeptide. Each of these peptides defined at least 1 non-crossreactive B cell epitope and contained T helper epitopes.

Abstract: The present invention provides a polypeptide SE36 derived from the N-terminal domain (47 kd) of SERA (serine-repeat antigen) produced by malaria parasite, Plasonodium falciparum, at the erythrocyte stage, a process for purifying said polypeptide, and a malaria vaccine and diagnostic agent using as an active component said purified antigen obtained therefrom. SE36 can be produced in Escherichia coli on a large scale by deleting all or part of polymerized serines of the 47 kd serine-repeat region, whereby high purification is permitted. The human IgG3 antibodies specifically binding to SE36 prevents highly effectively growth of the protozoa in the red blood cells to inhibit fever and cerebral malaria, and further prevent the death.

Abstract: The present invention relates to an in vitro diagnostic method for malaria in an individual comprising placing a tissue or a biological fluid taken from an individual in contact with a molecule or polypeptide composition, wherein said molecule or polypeptide composition comprises one or more peptide sequences bearing all or part of one or more T epitopes of the proteins resulting from the infectious activity of P. falciparum, under conditions allowing an in vitro immunological reaction to occur between said composition and the antibodies that may be present in the tissue or biological fluid, and in vitro detection of the antigen-antibody complexes formed. The invention further relates to a polypeptide comprising at least one T epitope from a liver-stage specific protein produced by P. falciparum and a vaccine composition directed against malaria comprising a molecule having one or more peptide sequences bearing all or part of one or more T epitopes resulting from the infectious activity of P.

Abstract: A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

Abstract: The present invention provides the RSP-1 and RSP-2 proteins which are involved in the cytoadhesion of P. falciparum during ring-stage infection of erythrocytes, antibodies which bind to the proteins, methods of screening for a P. falciparum infection, methods of determining the infective stage of P. falciparum and vaccines for protecting individuals from Plasmodium sp. infections.

Abstract: A combination kit for the treatment of malaria caused by Plasmodium vivax (P. vivax) having individual doses of an anti-malarial agent, 3-[1-[[4-[(6-methoxy-8-quinolinyl)amino]pentyl]amino]ethylidene]-dihydro-2(3H)-furanone (I) in the form of capsules; individual doses of the anti-malarial agent, chloroquine in the form of tablets; and instruction material for the administration of the two anti-malarial drugs. The combination kit is particularly suited for a 6 days treatment regimen where the treatment is rendered by five tablets containing 500 mg of chloroquine phosphate (equivalent to 300 mg base), three to be taken on day one and one each on days two and three; and five capsules containing 25 mg of 3-[1-[[4-[(6-methoxy-8-quinolinyl)amino]pentyl]amino]ethylidene]-dihydro-2(3H)-furanone (I), one each to be taken on days two to six.

Abstract: Described is a method for making a pharmaceutical preparation comprising the solubilisation of a peptide mixture, characterized in that the peptide mixture is solubilized by an aqueous solution containing at least one organic acid selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid and halogenated or hydroxylated forms thereof.

Abstract: The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of malarial surface protein MSP-1 which is known to be difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred protein candidates for expression using the recombinant techniques of the invention are MSP-1 proteins expressed from DNA coding sequences comprising reduced overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the native MSP-1 gene.