Abstract: A method of generating an antibody and cellular immune response against a Plasmodium in a primate, comprising administering at least 103 genetically modified live Plasmodium to the primate, wherein the genetically modified live Plasmodium is a species selected from Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium knowlesi, Plasmodium coatneyi, Plasmodium cynomolgi, and Plasmodium simium, and wherein the genetically modified live Plasmodium does not produce functional histamine releasing factor (HRF) protein, to thereby induce an antibody and cellular immune response against the Plasmodium in the primate. In some embodiments at least 104 genetically modified live Plasmodium is administered to the primate.

Abstract: The disclosure generally provides a WRrNYVAC comprising multiple antigens from different stages of a malaria parasite (Plasmodium) life cycle, methods for producing them, immunogenic vaccine formulations comprising WRrNYVAC, such as P. vivax containing formulations (WRPvrNYVAC) and P. falciparum containing formulations (WRPfrNYVAC) and methods for the prevention and/or treatment of malaria infections and poxvirus infections.

Abstract: Provided are compositions and methods of selecting at least three fragments one each from three domains of the malarial CSP for generating antigen specific CD8 effector T cells and non-cross reacting neutralizing antibody immune responses to the malarial parasite, which when administered prevent an infection of a human being when bitten by a malaria infected mosquito. The composition and method comprises priming an individual by administering a mixture of one or more adenoviral expression vectors encoding one or more fusion proteins, which comprises the malarial CSP antigen fragments linked to the extracellular domain of the CD40 ligand. The adenoviral expression vector comprises a transcription unit encoding a secretable fusion protein, the fusion protein containing selected malarial sporozoite CSP antigen fragments linked to the CD40 ligand to block the attachment to or infection of the human liver cell(s) by the malarial sporozoite.

Abstract: The present invention provides novel nucleotide sequence and other constructs used for expression of novel recombinant P. falciparum circumsporozoite proteins in bacterial cells such as E. coli. Processes are provided for producing a soluble recombinant P. falciparum CSP from E. coli. Methods to produce a human-grade, highly immunogenic anti-malaria vaccine based on CSP are shown. The novel recombinant P. falciparum circumsporozoite protein by itself or in combination with other malaria antigens or adjuvants can form the basis of an effective malaria vaccine.

Abstract: Disclosed herein are mutant Plasmodium-species parasites that are genetically attenuated (GAP). They retain the ability to infect a host and invade host hepatocytes but subsequently their development is completely arrested within the liver stage of Plasmodium development and the parasites do not reach the blood stage of development. Vaccines and pharmaceutical compositions comprising genetically attenuated Plasmodium sporozoites as well as methods of using the same are likewise provided.

Abstract: An immunogenic composition for use as a blood-stage malaria vaccine, a method of producing the immunogenic composition and a method of treatment of malaria are provided. The immunogenic composition includes isolated or purified merozoites, or red blood cells infected with merozoites, treated with centanamycin or tafuramycin A. The immunogenic composition does not include an adjuvant. A single dose of the immunogenic composition is sufficient to protect an animal against subsequent malaria infection by the same isolate, strain or species of Plasmodium used in the immunogenic composition, or by one or more heterologous isolates, strains or species of Plasmodium.

Abstract: This disclosure provides antibodies that are useful for preventing and/or treating malaria. The epitope to which the antibodies bind is in close proximity to the conserved proteolytic cleavage site of P. falciparum circumsporozoite protein (CSP), and the antibodies provided in this disclosure can prevent cleavage and inhibit P. falciparum sporozoites from invading the liver.

Abstract: A combined measles-malaria vaccine containing different attenuated recombinant measles-malaria vectors comprising a heterologous nucleic acid encoding several Plasmodium falciparum antigens is described. Preferably, it relates to viral vectors that comprise nucleic acids encoding the circumsporozoite (CS) protein of P. falciparum, the merozoite surface protein 1 (MSP-1) of P. falciparum, and its derivatives (p-42; p-83-30-38) in its glycosylated and secreted forms, and apical membrane antigen1 (AMA1) of P. falciparum, in its anchored or secreted form. The viral vector stems from an attenuated measles virus, based on a strain that is used as a vaccine and is efficient in delivering the gene of interest and that binds to and infects the relevant immune cells efficiently.

Abstract: Disclosed herein are pharmaceutical compositions comprising Plasmodium sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range Plasmodium and analogues of ?-galactosylceramide (?-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.

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: Described are methods for inducing an immune response in a subject against an antigen from a malaria-causing parasite, preferably P.

Abstract: A combined measles-malaria vaccine containing different attenuated recombinant measles-malaria vectors comprising a heterologous nucleic acid encoding several Plasmodium falciparum antigens is described. Preferably, it relates to viral vectors that comprise nucleic acids encoding the circumsporozoite (CS) protein of P. falciparum, the merozoite surface protein 1 (MSP-1) of P. falciparum, and its derivatives (p-42; p-83-30-38) in its glycosylated and secreted forms, and apical membrane antigen1 (AMA1) of P. falciparum, in its anchored or secreted form. The viral vector stems from an attenuated measles virus, based on a strain that is used as a vaccine and is efficient in delivering the gene of interest and that binds to and infects the relevant immune cells efficiently.

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 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: An adenoviral vector comprising a promoter further comprising a fragment of the 5? untranslated region of the CMV IE1 gene including intron A and a nucleic acid sequence encoding a pathogen or tumor antigen for use as a medicament.

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: An aqueous composition having increased protein stability is obtained by: a. determining a pH at which the protein has stability at the desired temperature; b. adding to the composition at least one displacement buffer wherein the displacement buffer has a pKa that is at least 1 unit greater or less than the pH of step (a); and c. adjusting the pH of the composition to the pH of step (a); wherein the aqueous composition does not comprise a conventional buffer at a concentration greater than about 2 mM and wherein the conventional buffer has a pKa that is within 1 unit of the pH of step (a).

Abstract: A method for inducing protective immunity in a vertebrate host against malaria, by administering to the host a live rodent Plasmodium organism and exploiting its cross-species protection potential. A method to use genetically engineered live rodent Plasmodium organisms expressing antigens from different stages of the life cycle of human-infective Plasmodium species to immunize vertebrate hosts against malaria. The invention further provides for the production of a vaccine composition, by suspending wild-type or genetically modified rodent Plasmodium organisms in a suitable pharmaceutically acceptable carrier solution.

Abstract: The present invention relates to peptides comprising at least one antigenic determinant or epitope of an apicomplexan Ferlin, Ferlin-like protein and/or another C2-domain containing protein for use as malaria vaccines. It further relates to compositions comprising said peptides and to the use of such compositions as malaria vaccines.

Abstract: Cloning and characterization of a TgIF2? kinase from Toxoplasma gondii designated TgIF2K-D illustrates that this protein is related to GCN2, an eIF2? kinase known to respond to nutrient starvation in other organisms. TgIF2K-D is present in the cytosol of both intra- and extracellular Toxoplasma and facilitates translational control through TgIF2? phosphorylation in extracellular parasites. Both a TgIF2K-D knockout parasite and a parasite harboring the TgIF2? mutant (S71A substitution) exhibited loss of eIF2? kinase activity which manifested itself as significant fitness defect. Accordingly, eIF2? phosphorylation and translational control are an important mechanism by which vulnerable extracellular parasites protect themselves which searching for a new host cell. TgIF2K-D is an excellent target for development of compounds and therapies that can be used to treat infections caused by Toxoplasma and other eukaryotic parasites, especially parasites that have high homology or identity to TgIF2K-D.

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: 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 provides an antigenically restricted subset of the highly variant PfEMP1 rosetting antigen which possess epitopes which may be exploited to raise immune responses effective against many diverse strains and isolates of the malaria parasite, Plasmodium falciparum. In this regard, the invention provides one or more P. falciparum Erythrocyte Membrane Protein-1 (PfEMP1) antigen(s) or a fragment or fragments thereof, for use in raising immune responses in humans.

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: 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: 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, inter alia, a method of raising an immune response against a pathogen which comprises administering (i) one or more first immunogenic polypeptides derived from said pathogen; (ii) one or more adenoviral vectors comprising one or more heterologous polynucleotides encoding one or more second immunogenic polypeptides derived from said pathogen; and (iii) an adjuvant; wherein the one or more first immunogenic polypeptides, the one or more adenoviral vectors and the adjuvant are administered concomitantly. The invention also relates to vaccines, pharmaceutical compositions, kits and uses employing said polypeptides, adenoviral vectors and adjuvants.

Abstract: The present invention relates to the use of vaccines with adjuvants comprising cationic liposomes where neutral lipids has been incorporated into the liposomes to change the gel-liquid phase transition and thereby modifying the IgG sub-type response and enhancing the CD8 response of the liposomal adjuvant. This technology can be used to increase the production of IgG2 antibodies. This sub-type of antibodies (IgG2 in mice corresponding to IgG3 in humans) have been shown to selectively engage Fc activatory receptors on the surface of innate immune cells leading to enhanced proinflammatory responses and thereby a more efficient immune response with higher levels of protection in animal models of e.g. malaria and Chlamydia. The use of adjuvants which selectively give rise to higher levels of IgG2 antibodies will improve the effect of vaccines e.g. against intracellular infections. Furthermore the technology can be used to induce a CD8 response which has been reported to improve the effect of vaccines against e.g.

Abstract: An immunogenic composition for use as a blood-stage malaria vaccine, a method of producing the immunogenic composition and a method of treatment of malaria are provided. The immunogenic composition includes isolated or purified merozoites, or red blood cells infected with merozoites, treated with centanamycin or tafuramycin A. The immunogenic composition does not include an adjuvant. A single dose of the immunogenic composition is sufficient to protect an animal against subsequent malaria infection by the same isolate, strain or species of Plasmodium used in the immunogenic composition, or by one or more heterologous isolates, strains or species of Plasmodium.

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 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: The present invention relates to preparations of substances in hydrophobic solvents in which they would not normally be soluble and to processes for obtaining these preparations. In particular, the invention relates to preparations of hydrophilic species in hydrophobic solvents such as oils. The use of these preparations as vaccines and in pharmaceutical compositions is also described.

Abstract: The present invention relates to novel compositions and methods for immunizing a host against malaria using a Plasmodium parasite genetically attenuated via the inactivation of the function of the hmgb2 gene.

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: Disclosed herein are pharmaceutical compositions comprising Plasmodium sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range Plasmodium and analogues of ?-galactosylceramide (?-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.

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: Disclosed and claimed is a method of non-invasive immunization in an animal and/or a method of inducing a systemic immune response or systemic therapeutic response to a gene product. The skin of the animal is contacted with a non-replicative vector chosen from the group of bacterium, virus, and fungus, wherein the vector comprises and expresses a nucleic acid molecule encoding the gene product, in an amount effective to induce the response.

Abstract: The present invention provides compositions and methods useful in the treatment or prevention of a condition caused by or associated with infection by Plasmodium falciparum, such as malaria. The compositions include various antigens of Plasmodium falciparum, both alone and in combination. The invention further includes fragments of the antigens.

Abstract: Immunogenic compositions and vaccines against Plasmodial infection comprising an Rh polypeptide or a fragment or variant thereof are disclosed. Also disclosed are Rh5 polypeptides or fragments or variants thereof capable of binding CD147 and conferring protection against infection and/or disease caused by multiple Plasmodial strains or Plasmodial species, inhibitors of the interaction between Rh5 and CD147 and methods for producing polypeptides in a mammalian expression system.

Abstract: The invention provides methods of treating or preventing malaria comprising administering to an animal an effective amount of a compound of formula (I): Q-Y—R1—R2 (I), wherein Q, Y, R1, and R2 are as described herein. Methods of inhibiting a plasmodial surface anion channel of a parasite in an animal are also provided. The invention also provides pharmaceutical compositions comprising a compound represented by formula (I) in combination with any one or more compounds represented by formulas II, V, and VI. Use of the pharmaceutical compositions for treating or preventing malaria or for inhibiting a plasmodial surface anion channel in animals including humans are also provided. Also provided by the invention are clag3 amino acid sequences and related nucleic acids, vectors, host cells, populations of cells, antibodies, and pharmaceutical compositions.

Abstract: The present invention relates to a method of coating a spore with one or more therapeutic agents. The present invention also relates to a coated spore obtained by the method of the present invention and the use of the coated spore as a vaccine.

Abstract: The present invention relates to immunogenic compositions for modulating the immune system, comprising a therapeutically effective quantity of two or more immuno-active antigenic agents with pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs) and one or more physiologically acceptable carriers, excipients, diluents or solvents. The immunogenic compositions according to the present invention are used for producing medicaments for preventing and/or treating, and for preventing and/or treating infectious diseases, auto-immune diseases, allergic diseases, inflammation, arthritis, inflammatory diseases, transplant rejection, affections caused by vascular disorders, diseases caused by haemorrhagic or ischaemic cardiovascular accidents, ischaemia, heart attack and haemorrhagia leading to tissue destruction, heart, kidney, respiratory or liver insufficiency, cancer, malign and benign tumours and neoplasia.

Abstract: The present invention relates to polypeptides or fragments thereof for use as malaria vaccines. It also relates to nucleic acid molecules coding for the polypeptides of the invention. It further relates to compositions comprising such polypeptides or fragments thereof or the nucleic acid molecules, in particular combinations of such polypeptides or fragments thereof, and the use of such compositions as malaria vaccines.

Abstract: Embodiments of the present invention concern methods of preventing malaria in a target population of humans comprising: uniformly administering a therapeutically effective amount of a live low dose malaria vaccine to each individual within the target population on each of two or three consecutive days. The methods include using Plasmodium infected mosquitoes to inject Plasmodium into individuals through mosquito bites.

Abstract: Provided herein is consensus amino acid sequences of P. falciparum (P.f.) proteins and their encoding sequences, as well as expression constructs expressing the sequences. Also provided herein are methods for generating an immune response against P. falciparum using the expression constructs provided herein.

Abstract: Multilayer films comprise polypeptide epitopes from Plasmodium falciparum, specifically a circumsporozoite T1, B or T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a Plasmodium protozoan.

Abstract: Disclosed are compositions and the use of the compositions for protection against pathogens comprising an isolated internal pathogenic protein, a TLR agonist and an aluminum salt.

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: 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.