Abstract: Isolated proteins and nucleic acid sequence encoding such protein that interacts with a red blood cell to be invaded by a malaria parasite and link with a component of the actin-myosin based machinery of the malaria parasite are provided. In addition methods for identifying agents which inhibit the function of these proteins as chemotherapeutic and/or immunologic agents for treatment and prevention of malaria infections are provided. Compositions for treatment and prevention of malaria infections and methods for preventing and treating malaria infections are also provided.

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: The present invention includes compositions and methods for the development and use of a vaccine that includes one or more FusM antigens in a carrier adapted to trigger a FusM-specific immune response in the human blood stream.

Abstract: Viral replicon selected nucleic acid expression libraries are useful for analyzing multiple antigens associated with a parasite, pathogen or neoplasia or for preparing immunogenic compositions for generating immune responses specific for the parasite, pathogen or neoplasia. Alphavirus replicon particles representative of the nucleic acid expression library are preferred. The nucleic acid library can be a random library, or it can be prepared after a selection step, for example, by differential hybridization prior to cloning into the replicon vector.

Abstract: A vaccine or immunogenic composition is described that contains recombinantly produced, secreted, forms of malaria MSP-1 C-terminal subunit proteins from any of the Plasmodium falciparum strains as active ingredients combined with one or more adjuvants. The immunogenic compositions that result in a protective response are based on the use of a single adjuvant that forms an emulsion or use of such emulsion in combination with a second adjuvant that is an immunomodulating agent. Such a vaccine elicits a strong immune response characterized by antibodies that are capable of inhibiting parasite growth in vitro as well as antibodies that are incapable of inhibiting parasite growth in vitro, but are capable of enhancing the activity of the inhibitory antibodies. The disclosed vaccine formulations are capable of generating a protective response against malaria in vaccinated subjects.

Abstract: The present disclosure provides methods for enhancing the response of a patient's immune system to vaccination. This is accomplished by reactivating the thymus. Optionally, hematopoietic stem cells, autologous, syngeneic, allogeneic or xenogeneic, are delivered to increase the speed of regeneration of the patient's immune system. In one embodiment the hematopoietic stem cells are CD34+. The patient's thymus is reactivated by disruption of sex steroid mediated signaling to the thymus. In one embodiment, this disruption is created by administration of LHRH agonists, LHRH antagonists, anti-LHRH receptor antibodies, anti-LHRH vaccines or combinations thereof.

Abstract: The present invention relates novel methods and compositions for blocking transmission of Plasmodium vivax which cause malaria. In particular, Pvs25 and Pvs28 polypeptides, variants, including deglycosylated forms, and fusion proteins thereof, are disclosed which, when administered to a susceptible organism, induce an immune response against a 25 kD and 28 kD protein, respectively, on the surface of Plasmodium vivax zygotes and ookinetes. This immune response in the susceptible organism can block transmission of malaria.

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: A composition comprising an oil in water emulsion and a saponin, wherein said oil is a metabolisable oil, and having an advantageous ratio of metabolisable oil:saponin (w/w).

Abstract: A vaccine formulation for the prevention or amelioration of plasmodium infection in humans is provided. The vaccine comprises a malaria antigen, especially a protein which comprises a portion of the CS protein of P. falciparum fused in frame via a linear linker to the N-terminal of HBsAg, and an immunostimulatory CpG oligonucleotide. Methods for making the vaccine formulation of the invention are described. Patients may also be treated by pre-administration of the CpG oligonucleotide prior to administration of the malaria antigen.

Abstract: The present invention relates to a novel use of a malaria antigen to immunise against malarial disease. The invention relates in particular to the use of sporozoite antigens, in particular circumsporozoite (CS) protein or fragments thereof, to immunise against severe malarial disease.

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 to nanoparticle vaccines comprised of a carrier, particularly polymerized lipids, having multiple copies of an antigen or combinations of different antigens displayed on the carrier. Such antigen-displaying nanoparticles may also display a targeting molecule on its surface in order to direct it to a specific site or cell type to optimize a desired immune response. The present invention also relates to encapsulating an antigen or combinations of different antigens within such nanoparticles, with or without a targeting molecule displayed on its surface. The antigens used in this invention are effective to produce an immune response against a variety of pathological conditions.

Abstract: The present invention relates to a fowlpox virus genome which has modifications in one or more wild-type FPV genes. The present invention also relates to a viral particle comprising such a genome and its use to deliver a nucleotide of interest (NOI) to a target cell. The present invention also relates to vaccination methods, particularly a method which comprises administering a priming composition (which comprises a first non-replicating viral vector) and a boosting composition (which comprises a second non-replicating viral vector) to a subject to treat and/or prevent a disease.

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: Disclosed are apparatuses and methods for the production of attenuated aseptic parasites in hematophagous insects generally, and production of Plasmodium species sporozoites in Anopheles species mosquitoes specifically; apparatuses and methods for the production of strains of hematophagous insects with desired properties such as hypoallergenicity or hyperinfectivity; methods of producing a parasite strain that is capable of withstanding cyropreservation at temperatures close to freezing; apparatuses and methods for the injection of an attenuated parasite vaccine; production of parasites and hematophagous insects that are free from contamination by unwanted biological agents; apparatuses for the reconstruction of complex parasitic life cycles aseptically to avoid the contamination of the parasite or the insect vector host with unwanted biological agents.

Abstract: The invention presents vaccine formulations comprising highly antigenic epitopes identified within the semi-conserved loop-I of domain III that are capable of eliciting parasite growth inhibitory antibodies. The cyclized or linear peptides can be applied by known adjuvants or be encapsulated by or attached onto the surface of liposomes or virosomes (IRIVs) which serve as human compatible antigen delivery systems. Both cyclized and linear versions of the peptide antigens are surprisingly effective in eliciting immune responses that are cross-reactive with parasite-expressed AMA-1.

Abstract: The present invention relates generally to a method for the prophylaxis and treatment of parasitic infections in animals and birds. More particularly, the present invention contemplates a method for the prophylaxis and treatment of Plasmodium infection in mammals and the prophylaxis and treatment of disease conditions caused or exacerbated by Plasmodium. Even more particularly, the present invention is directed to a method for the prophylaxis and treatment of malaria including ameliorating the clinical effects of malaria and agents useful for same.

Abstract: In this application is the expression and purification of a recombinant Plasmodium vivax (SalI) PvMSP-1 p42. The method of the present invention produces a highly purified protein which retains folding and disulfide bridging of the native molecule. The recombinant PvMSP-1 p42 is useful as a diagnostic reagent, for use in antibody production, and as a vaccine.

Abstract: The present invention relates to carbohydrates capable of acting as receptors for malaria antigens present on the surfaces of malaria infected erythrocytes. The receptors according to the invention comprises negatively charged glycosaminoglycan-like moities, preferably sulphated. The invention also relates to novel malaria polypeptides capable of acting as ligands in relation to the receptors according to the invention. The invention also encompasses the use thereof as medicaments, pharmaceutical compositions containing the same as well as antibodies directed against said new ligands.

Abstract: The invention provides a fusion protein comprising the Plasmodium merozoite surface protein-1 (MSP1) and the Plasmodium apical membrane antigen 1 (AMA-1), the encoding DNA sequence, the vector containing the sequence, the host cell containing the vector, and the genetic engineering method for preparing the fusion protein and the usage for producing anti-malarial vaccine. The AMA-1/MSP1 fusion protein of the present invention has excellent immunogenicity and can cause an effective immune response against Plasmodium in individuals.

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 non-naturally occurring variant of a C-terminal fragment of a Plasmodium merozoite surface protein-1 (MSP-1) wherein said variant has (i) a reduced affinity, compared with a naturally occurring Plasmodium MSP-119, for at least one first antibody capable of blocking the binding of a second antibody, which second antibody inhibits the proteolytic cleavage of Plasmodium MSP-142 and (ii) substantially the same affinity for at least one third antibody compared with said naturally occurring Plasmodium MSP-119. which third antibody inhibits the proteolytic cleavage of Plasmodium MSP-142 is provided for use in an anti-malarial vaccine.

Abstract: Synthetic gene sequences encoding erythrocyte binding protein of a malaria pathogen for the expression of the erythrocyte binding protein. The codon composition of the synthetic gene sequences approximates the mammalian codon composition. The synthetic gene sequences are useful for incorporation into the DNA vaccine vectors, for the incorporation into various expression vectors for production of malaria proteins, or both. The synthetic genes may be modified to avoid post-translational modification of the encoded protein in hosts. Administration of the synthetic gene sequences, or the encoded protein, as an immunization agent is useful for induction of immunity against malaria, treatment of malaria, or both.

Abstract: The present invention relates to immunogenic compositions comprising as an immunogen a long synthetic or recombinant peptide of a merozoite surface protein 3b (MSP-3b) peptide, an MSP-3c peptide and a MSP-3d peptide. Vaccines against malaria are also disclosed using these peptides alone or in combination with a pharmaceutically acceptable carrier.

Abstract: The present invention provides novel assay systems and methods for monitoring cell invasion by protozoal parasites. The present invention further provides methods of using these assays systems to identify compounds that treat or prevent protozoal infection. The present invention further provides pharmaceutical compositions that have anit-protozoal activity and methods of treating infections.

Abstract: Polypeptide molecules containing at least 10 consecutive amino acids of the amino acid sequence shown in FIG. 2, representing the LSA3 antigen, the following peptides being excluded: RDELFNELLNSVDVNGEVKENILEESQVNDDIFNSLVKSVQQEQQHNVEE VEESVEENDEESVEENVEENVENNDDGSVASSVEESIASSVDESIDSSIE- ENVAPTVEEIVAPTVEEIVAPSVVEKCAPSVEESVAPSVEESVAEMLKER (729S) RDELFNELLNSVDVNGEVKENILEESQVNDDIFNSLVKSVQQEQQHN DELFNELLNSVDVNGEVKENILEESQ, (NRI) LEESQVNDDIFSNSLVKSVQQEQQHNV, (NRII) VESVAPSVEESVAPSVEESVAENVESSV.

Abstract: In this application is described the expression and purification of a recombinant Plasmodium falciparum (3D7) AMA-1 ectodomain. The method of the present invention produces a highly purified protein which retains folding and disulfide bridging of the native molecule. The recombinant AMA-1 is useful as a diagnostic reagent, for use in antibody production, and as a protein for use alone, or as part of, a vaccine to prevent malaria.

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: A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid protein (HBc) is disclosed that contains an immunogen for inducing the production of antibodies to malarial proteins. An immunogenic malarial epitope is expressed between residues 78 and 79 of the HBc immunogenic loop sequence. The chimer preferably contains a malaria-specific T cell epitope and is preferably engineered for both enhanced stability of self-assembled particles and enhanced yield of those chimeric particles. Methods of making and using the chimers are also disclosed.

Abstract: The present invention relates to the discovery of a var gene and corresponding protein that modulates adhesion of parasitized red blood cells to chondroitin sulfate A. Novel biological tools, prophylactics, therapeutics, diagnostics, and methods of use of the foregoing are also disclosed.

Abstract: 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 is directed to isolated nucleic acid molecules encoding Plasmodium sp. chitinases. Expression vectors and host cells comprising the nucleic acid molecules are also provided, as well as methods for increasing or decreasing the expression of the chitinase in host cells. The invention further provides methods of screening a substance for the ability of the substance to modify chitinase function, and a method for isolating other chitinase molecules. DNA oligomers capable of hybridizing to the nucleic acid molecule encoding the chitinase are provided, which can be used to detect chitinase in a sample. An isolated Plasmodium sp. chitinase is also provided. Antibodies specific for the chitinase, and fragments thereof, are provided, as are compositions comprising the chitinase and a compatible carrier. The subject invention further provides methods of preventing infection of mosquitoes by Plasmodium sp. and methods of preventing transmission of malaria.

Abstract: The present invention relates to a process for the preparation of a vaccine against tuberculosis and other intracellular pathogens, this vaccine is targeted against intracellular pathogens, more particularly the pathogen Mycobacterium tuberculosis and Salmonella in this case.

Abstract: The present invention relates to transmission blocking vaccines against malaria. Vaccines of the present invention contain a recombinant virus encoding all, or a unique portion, of the 25 kDa sexual stage surface protein of Plasmodium falciparum, Pfs25, or the Pfs25 protein purified from host cells infected with the above-described recombinant virus. Mice inoculated with the recombinant virus developed antibodies with transmission blocking activity. The present invention also relates to recombinant viruses used in the vaccines of the present invention, host cells infected with the recombinant viruses of the present invention and methods of preventing or treating malarial infections using the vaccines of the present invention.

Abstract: An animal model for CNS infection by Apicomplexan parasites was produced by inoculating a homologous cell or other type of cell with the merozoite stage of the Apicomplexan parasite and inoculating the infected homologous cell or a cell line prepared therefrom back into the host from which it came. Such a model was used to develop drugs for treatment or prophylaxis, vaccines for protection from Apicomplexan diseases and diagnostic tests for determination active infection with Apicomplexan parasites.

Abstract: The present invention provides methods and compositions for eliciting protective immunity against malaria. In particular, the invention relates to universal T-cell epitopes that elicit T-cell responses in individuals of differing genetic backgrounds. Immunogenic compositions and vaccines including malaria-specific universal T-cell epitopes are disclosed.

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: A vaccine composition useful in the prevention or treatment of malaria comprises a plurality of malaria-derived antigens in combination with an adjuvant which is a preferential stimulator of TH1 cell response,

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.

Abstract: The present invention relates to a vaccine against malaria comprising a polypeptide having the amino acid sequence of the C-terminal part of the circumsporozoite protein of a Plasmodium species, in which polypeptide one or more pairs of cysteine residues are oxidized, and optionally a suitable carrier and/or adjuvant and/or biodegradable microcapsules for use in humans.

Abstract: Proteins from the merozoite stage of the malaria parasite, fragments and derivatives thereof, DNA coding for the said proteins, and processes for the preparation of the proteins and plasmid and viral vectors useful in said processes. The invention also provides antibodies to the proteins and immunological compositions containing the proteins.

Abstract: This invention relates to a vaccine composition useful in the prevention or treatment of malaria comprises a plurality of malaria-derived antigens in combination with an adjuvant which is a preferential stimulator of TH1 cell response.

Abstract: The present invention provides compositions of matter comprising a polypeptide expressed from insect cells harboring a baculovirus vector the encodes the polypeptide, wherein the polypeptide comprises amino acid sequences derived from the p42 fragment of the Plasmodium falciparum gp 195 protein or derivatives thereof. Such compositions of matter find use for example for inducing the production of anti-p42 antibodies both in vivo and in vitro.

Abstract: An immunogenic polypeptide for use in inducing an immune response against Plasmodium infection comprises an amino acid sequence corresponding to a non-full length fragment of the apical membrane antigen 1 (AMA-1) of Plasmodium species which does not include a transmembrane domain thereof, and which is stabilised by folding thereof. Production of the immunogenic polypeptide by expression of a recombinant DNA molecule in a host cell, and methods and compositions using the immunogenic polypeptide are disclosed.

Abstract: Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers.

Abstract: A Plasmodium falciparum gene encoding immunogenic SERA protein has been isolated by a) systematically screening a lambda gt11 recombinant DNA expression library with a murine monoclonal antibody directed against protein antigens of this pathogen, and b) systematically screening a lambda gt11 genomic cDNA and oligonucleotide probes directed against this pathogen. A 111 kDa protein has been shown to have immunogenic activity against parasite inhibitory antibodies. The gene encoding this protein, including the signal sequence and regulatory sequence in the adjacent 5′ flanking sequence has been isolated and sequenced. Isolation and characterization of genes encoding major protein antigens of P. falciparum make it possible to develop reagents useful in the diagnosis, prevention and treatment of malaria. In addition, the signal sequences or regulatory sequences of this gene can be used to stimulate the production of other useful genetic products.

Abstract: The invention discloses a molecule or polypeptide composition characterized by the presence in its structure of one or more peptide sequences bearing all or part of one or more T epitopes, and possibly other epitopes, particularly B epitopes, characteristic of proteins resulting from the infectious activity of P. falciparum in hepatic cells.