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: The present invention relates to an attenuated Plasmodium parasite having a genome comprising a non-reversible knockout of the PyPNP gene, a vaccine derived therefrom, and related methods and uses.

Abstract: The present invention discloses a composition comprising an immunogenic sequence or a fragment thereof and TEM8 or a fragment thereof, where the TEM8 or the fragment functions as an adjuvant and enhances the eilicitation of immune responses mediated by the immunogenic sequence or the fragment thereof. Also disclosed herein is the use of such compositions in the treatment of cancer or pathogen associated diseases.

Abstract: This invention provides compositions for inducing an immune response in a vertebrate host against a protozoan parasite. In certain embodiments the composition comprises a protozoan parasite comprising a psoralen-modified DNA, whereby said protozoan parasite is killed but metabolically active (KBMA); and optionally a Toll-like receptor agonist.

Abstract: Here we identify MMG and its alpha- and ketomycolic acid derivatives as highly bioactive lipids derived from M. bovis BCG (Copenhagen) capable of stimulating and activating human DC's at exceedingly low doses. In addition to their direct role as immunostimulators of human DC's we demonstrate their use in the development of a new generation of adjuvants suitable for human administration. We furthermore identify a number of highly active synthetic MMG analogues with great potential in cancer treatment, and for vaccine adjuvants against both infectious disease and disorders like Alzheimers disease.

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: Provided is a polypeptide composition comprising one or more polypeptides, which polypeptides are immunogenic in a vertebrate such that they cause the vertebrate to produce immune system cells capable of recognising at least one epitope from an arthropod saliva protein fraction, wherein the arthropod saliva protein fraction has a mass of 40 kDA or less, and wherein the polypeptides are selected independently from: the polypeptide sequences of SEQ ID 1-44 or sub-sequences from these sequences, the sub-sequences having 7 amino acids or more; or from polypeptide sequences having 85% homology or more with one or more of the above sequences and contained in one or more of the following databases: GenBank, Protein Data Bank (PDB), SwissProt, Protein Information Resource (PIR), Protein Research Foundation (PRF), or CDS translations of these.

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 invention relates to a recombinant protein fabricated in a baculovirus system, of which the essential constitutive polypeptide sequence is that of a C-terminal fragment of 19 kilodalton (p19) of the surface protein 1 (protein MSP-1) of the merozoite parasite of the Plasmodium type, particularly Plasmodium falciparum, which is infectious for humans, said C-terminal fragment remaining normally anchored at the surface of the parasite at the end of its penetration phase into human erythrocytes, in the occurrence of an infectious cycle. Said recombinant protein is applicable to the production of vaccines against malaria.

Abstract: The invention provides a method of inducing an immune response against malaria in a mammal. The method comprises intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of (a) a first adenoviral vector comprising a nucleic acid sequence encoding a P. falciparum circumsporozoite protein (CSP) operably linked to a human CMV promoter, and/or (b) a second adenoviral vector comprising a nucleic acid sequence encoding a P. falciparum apical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter.

Abstract: The present invention relates to novel antigens involved in gestational malaria, and more particularly to polynucleotide and polypeptide sequences, conjugates, cloning vectors including said sequences for the preparation of immunogenic compositions and vaccines, antibodies, and to the use thereof for treating gestational malaria. The invention also relates to diagnostic methods and kits.

Abstract: The present invention is directed to novel polynucleotides and polypeptides directed to EXP1 of Plasmodium vivax, and methods of using these polynucleotides and polypeptides in the detection of P. vivax antibodies or anti-P. vivax antibodies in a subject. The invention finds particular useful application in identifying recent exposure to P. vivax.

Abstract: Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (?-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.

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 invention is directed to novel synthetic C-glycolipids that selectively induce a ThI-type immune response characterized by enhanced IL-12 secretion and increased activation of dendritic cells. The compounds of the invention are thereby useful in treating infections, cancers, cell proliferative disorders, and autoimmune diseases, both directly and as adjuvants.

Abstract: The present invention relates to liposome formulations that are physically stable. In particular the present invention relates to steric stabilization of cationic liposomes by incorporating glycolipids into the liposomes. The stabilized liposomes can be used either as an adjuvant for antigenic components or as a drug delivery system. In particular the invention relates to vaccines with adjuvants in aqueous media for immunization, where the final product is stable.

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 pertains to the protection against malaria. More particularly, the invention is based on the characterization of a novel liver and sporozoite-stage P. falciparum antigen, referred to as LSA-5. This antigen is highly antigenic and the prevalence of antibodies in subjects living in endemic areas is extremely high (ca. 90%). The invention concerns antigenic peptides, mixtures thereof, or polypeptides, mixotopes and conjugates comprising part of the sequence of LSA-5, as well as immunogenic compositions, vaccines and kits comprising these.

Abstract: The present invention provides an easy and rapid method for detecting/identifying the presence or absence of specific Plasmodium parasites and four species of malaria parasites in a human specimen, an anti-malaria measure support system, and a malaria infection-prevention/treatment system, which can contribute to practical diagnosis in a malaria endemic area. According to the present invention, using a genus-specific primer set that can detect four Plasmodium parasites that infect humans at a time, and the primer sets each specific to each of four species of Plasmodium parasites (P. falciparum, P. vivax, P. malariae, and P. ovale), the presence or absence of infection with these parasites can be detected/identified easily and rapidly.

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: Disclosed are substantially purified Plasmodium sporozoites and preparations of Plasmodium sporozoites substantially separated from attendant non-sporozoite material, where the preparations of Plasmodium sporozoites have increasing levels of purity. Vaccines and pharmaceutical compositions comprising purified Plasmodium sporozoites are likewise provided. Methods of purifying preparations of Plasmodium sporozoites are also provided.

Abstract: The invention provides isolated placental P. falciparum polypeptides comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:1-4 and 6-24, and immunogenic derivatives thereof. The invention also provides isolated nucleic acid molecules encoding the placental P. falciparum polypeptides of the invention, compositions comprising one or more placental P. falciparum polypeptides of the invention, methods for inducing an immune response against the placental P. falciparum polypeptides, and methods for treating and diagnosing placental malaria.

Abstract: The present invention features methods and compositions related to chitosan antigen depots, and chitosan cytokine depots, and the use of depot compositions in treating and preventing diseases.

Abstract: The present invention relates to a malaria vaccine for administration to a host, comprising an attenuated malarial parasite with a gene that 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/or for infection of host red blood cells. The gene that has been rendered non-functional can be, e.g., a gene that encodes a nutrient transporter protein or a gene that encodes an enzyme involved in phospholipid biosynthesis. The invention also provides kits and methods that include such attenuated malarial parasites.

Abstract: Accordingly, the invention provides constructs in which the nucleic acids encoding Plasmodium falciparum MSP4 and MSP5, and the resulting polypeptides, have been modified. More particularly, this invention provides constructs encoding recombinant MSP4 and MSP5 polypeptides, which are expressed as soluble, secreted polypeptides in a baculovirus-insect cell expression system. It was surprisingly found that the recombinant polypeptides contain an EGF-like domain at the C-terminus that is properly folded in the polypeptide.

Abstract: The present invention relates to a novel hybrid/fusion protein derived from the CS protein of Plasmodium vivax (P. vivax), methods for preparing and purifying the same, its use in medicine, particularly in the prevention of malarial infections, for example those caused by P. vivax, compositions/vaccines containing the protein or antibodies against the protein such as monoclonal or polyclonal antibodies and use of the same, particularly in therapy. The invention also extends to lipoprotein particles of said hybrid protein and formulations/vaccines comprising the same and use thereof. In particular it relates to an immunogenic hybrid fusion protein comprising: a. at least one repeat unit derived from the repeating region of a type I circumsporozoite protein of P. vivax, b. at least one repeat unit derived from the repeating region of a type II circumsporozoite protein of P. vivax, and surface antigen S derived from Hepatitis B virus, or a fragment thereof.

Abstract: The invention relates to a digalactolipidic antigen exposed on the surface of apicomplex parasites, in the form of a vegetable-type digalactoglycerolipid, and adapted for inducing the production of specific antibodies capable of inhibiting the proliferation and/or the invasive properties of said parasites; the invention also relates to a derived antibody or functional antibody fragment, and to their diagnostic, immunotherapeutic and vaccine applications in human beings or animals.

Abstract: Disclosed herein are immunogenic compositions comprising a multilayer film comprising two or more layers of polyelectrolytes, wherein adjacent layers comprise oppositely charged polyelectrolytes. A first layer polyelectrolyte comprises an antigenic polypeptide comprising one or more surface adsorption regions covalently linked to one or more antigenic determinant regions, wherein the antigenic polypeptide and the one or more surface adsorption regions have the same polarity. The immunogenic compositions may be employed in methods of eliciting an immune response in a vertebrate organism.

Abstract: The invention provides isolated placental P. falciparum polypeptides comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:1-4 and 6-24, and immunogenic derivatives thereof. The invention also provides isolated nucleic acid molecules encoding the placental P. falciparum polypeptides of the invention, compositions comprising one or more placental P. falciparum polypeptides of the invention, methods for inducing an immune response against the placental P. falciparum polypeptides, and methods for treating and diagnosing placental malaria.

Abstract: The present invention relates to an immuno-therapeutic and prophylactic vaccine comprising monocytes or immature myeloid cells (IMCs) loaded with the ligand of natural killer T cell and an antigen for the prevention and treatment of infectious disease or cancer, more precisely, an immuno-therapeutic and prophylactic vaccine comprising monocytes or IMCs loaded with ?-galactosylceramide (?GalCer), a kind of glycolipid and a natural killer T cell ligand, and antigen. Monocytes or immature myeloid cells (IMCs) therein, which are easily obtainable, unlike dendritic cells, not only induce a significant level of cytotoxic T lymphocyte responses but also have a prophylactic and therapeutic effect on malignant tumor. Therefore, the immuno-therapeutic and prophylactic vaccine of the present invention can be effectively used as an immunotherapeutic agent.

Abstract: Peptides of influenza virus hemagglutinin protein and Plasmodium falciparum malaria antigen, antibodies specific for the peptides, influenza vaccines, malaria vaccines and methods of stimulating the immune response of a subject to produce antibodies to influenza virus or malaria are disclosed. Also disclosed are methods for formulating vaccines for influenza virus.

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 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: 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 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: 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 is related to the identification of CSA binding domains in var2CSA homologs from different parasite strains and furthermore to an isolated polypeptide comprising a CSA-binding domain sequence substantially as shown in SEQ ID NO:1, or functional equivalent thereof, or the corresponding portion of PfEMP1 from a strain of Plasmodium, substantially in isolation from sequences naturally occurring adjacent thereto in the PfEMP1 protein, and related nucleotide sequences, vectors, host cells, vaccines, and methods of use.

Abstract: The invention provides an immunogenic composition comprising MSP-8 linked to an antigen. Methods of using the composition to induce an immune response in an animal are also provided.

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: This invention relates generally to the field of pathogen peptidic antigens and their use, for example, for the preparation of a vaccine against said pathogen. More specifically, the present invention relates to an antigenic peptide deriving from Plasmodium species sequences, and includes antibodies and methods of producing and using same.

Abstract: The instant invention is to provide a method for detecting and measuring malaria infection utilizing the induction by hemozoin (HZ); a method for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection using the method for detecting and measuring; and a means for regulating the induction of innate immunity using the HZ, synthetic HZ, or derivatives thereof as an adjuvant or immunostimulant. Malaria infection is detected and measured of by detecting and measuring HZ-induced, TLR9-mediated, and MyD88-dependent innate immune activity. The detection and measurement of malaria infection can be used to diagnose malaria infection. The method for detecting and measuring is also used for screening a vaccine for malaria infection and a preventative or therapeutic agent for malaria infection. Further, HZ, synthetic HZ, or derivatives thereof are used as an adjuvant or immunostimulant to regulate HZ-induced innate immune induction.

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 methods of identifying lethal, virulent and rapidly replicating viruses, organisms, and malignancies comprising comparing Replikin concentrations among different viruses, organisms, or malignancies. The present invention further provides isolated Replikin Peak Genes associated with increased lethality, virulence and rapid replication, for diagnostic, therapeutic and predictive purposes.

Abstract: The invention concerns mixed micelles or micro-aggregates for inducing an immune response containing at least a first lipopeptide comprising a CTL epitope and at least a first lipid motif; and a second lipopeptide comprising at least an auxiliary T epitope and at least a lipid motif, whereof the type can be different from the first lipopeptide motif. Said micelles can be used as medicines and vaccines.

Abstract: There is provided, inter alia, a method for the prophylaxis of productive malaria infection in travelers to endemic regions comprising the administration of suitable amounts of a formulation comprising a Plasmodium antigen or an immunogenic fragment or derivative thereof and an adjuvant, comprising a lipid A derivative and a saponin in a liposome formulation.

Abstract: The invention provides a product which comprises a C4bp core protein and a monomeric antigen, desirably in the form of a fusion protein. Monomeric antigens include malarial and influenza antigens. The C4bp core protein provides for assembly of multimeric complexes of the monomeric antigen, or mixtures thereof. The complexes are useful as vaccines.

Abstract: The present invention relates to adjuvant compositions which are suitable to be used in vaccines. In particular, the adjuvant compositions of the present invention comprises a saponin and an immunostimulatory oligonucleotide, optionally with a carrier. Also provided by the present invention are vaccines comprising the adjuvants of the present invention and an antigen. Further provided are methods of manufacture of the adjuvants and vaccines of the present invention and their use as medicaments. Methods of treating an individual susceptible to or suffering from a disease by the administration of the vaccines of the present invention are also provided.

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: An immunogenic composition in a dose volume suitable for human use comprising an antigen or antigenic preparation, in combination with an adjuvant which adjuvant comprises an immunologically active saponin fraction derived from the bark of Quillaja Saponaria Molina presented in the form of a liposome and a lipopolysaccharide wherein said saponin fraction and said lipopolysaccharide are both present in said human dose at a level of below 30 ?g.