35 results about "Malarial Vaccines" patented technology

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.

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.

The present invention provides a particle comprising a polypeptide and at least one malaria antigen, and a composition or vaccine comprising thereof, its use in medicine, particularly in the prevention or treatment of malaria infections.

Disclosed herein are diagnostic assays for identifying individuals that are protected against Plasmodium falciparum caused malaria. Such assays are particularly useful for determining not only the protective efficacy of Pf whole parasite vaccines for individual subjects, but also within populations of vaccinated subjects. The assays comprise the use of proteomes representing at least 50% of Pf, preferably coupled to a solid phase as a fixed array. The arrays are used to probe the sera of human subjects, particularly subjects of human clinical trials of whole parasite malaria vaccines as well as public health vaccination campaigns. Serum samples with antibody profiles most strongly reactive in multiplex to CSP and MSP5 demonstrate a sensitivity of from 92% to 100% and a specificity of from 84% to 89%.

An object of the present invention is to provide a means for producing an antigenic component with the retained native antigenicity using a cell-free protein synthesis. In particular, it is an object to provide a means for producing an antigenic component without depending on codon usage, like expressing an antigenic component from a gene containing a large amount of AT. The present inventors have made a strenuous study to solve the matters described above and successfully completed the present invention by preparing an antigenic component with the retained antigenicity, in particular a malaria antigen useful for manufacturing a malaria vaccine, through a system with the use of a wheat embryo among cell-free protein synthesis means.

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.

The technology provided herein relates to novel malaria vaccines composed of different recombinant proteins, in particular recombinant fusion proteins comprising several different Plasmodium falciparum antigens from the pre-erythrocytic, the blood, and the sexual parasite main stages. The proteins may be used in a mixture vaccine formulation to elicit protective immune responses in humans. Nucleic acid molecules encoding said recombinant proteins, vectors and host cells containing the nucleic acids and methods for preparation and producing such proteins are also disclosed, as well as antibodies induced or generated by the use of said malaria vaccines and the use of such antibodies or recombinant derivatives for passive immunotherapy.

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.

The present invention relates to combinations of polypeptides or of polynucleotides corresponding to a specific region of the N-terminal portion of the VAR2CSA protein of different parasitic families or lines of Plasmodium falciparum, and to their use in the prevention of pregnancy-associated malaria. The invention also relates to immunogenic compositions and to vaccines useful for preventing malaria in pregnant women.

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.

The invention provides a recombinant vector, a recombinant baculovirus prepared with the vector and application of the virus in preparation of malaria vaccines. The recombinant vector is constructed by inserting a section of recombinant sequence into the pFastBacDual vector. The recombinant sequence is formed by: according to CMV, Ph, SP and TM sequences, adding EcoR I enzyme site and Xho I enzyme site between SP and TM, adding KpnI enzyme site in front of CMV-F, and adding HindIII enzyme site after TM-R. The recombinant baculovirus is obtained by: inserting Plasmodium yoelii Pys25 antigen gene into the recombinant vector, conducting homologous recombination with the genome of a shuttle vector Bacmid through transposition, then transfecting a bombyx mori cell, and performing packaging in the bombyx mori cell. Through simple separation and purification of the recombinant baculovirus, an antibody with good titer can be prepared, thus providing a reference for study of P25 malaria vaccines.

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.

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.

A fusion protein, from P. falciparum Glutamate-rich protein(GLURP) genetically coupled to P. falciparum Merozoite surface protein 3 (MSP3) was produced in Lactococcus lactis as a secreted recombinant GLURP-MSP3 hybrid protein and experiments showed that the GLURP-part of the hybrid increased the overall antibody response. Immunizations with the hybrid protein consistently generated a stronger antibody response against the individual GLURP and MSP3 domains than a mixture of the two recombinant molecules injected at one site or the individual recombinant molecules injected simultaneously at two different sites. The difference was most pronounced for the MSP3-specific antibody response suggesting that T cell epitopes located in the GLURP RO-region provide help for B-cell epitopes in the MSP3 region. Moverover, when the animals were injected with a mixture of GLURP and MSP3, individual mice tended to mount a predominant antibody response against either molecule: in some animals GLURP was immunodominant whereas in other animals MSP3 was the dominant immunogen. Additionally, the hybrid was also more antigenic than the individual recombinant proteins since the ELISA-titer of naturally occurring IgG antibodies, in clinically

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.

The present disclosure relates to novel malaria vaccines composed of different recombinant proteins, in particular recombinant fusion proteins comprising several different Plasmodium falciparum antigens from the pre-erythrocytic the blood, and the sexual parasite stages. The proteins and / or fusion proteins will be used in a mixture vaccine formulation to elicit protective immune responses in humans. Nucleic acid molecules encoding said recombinant proteins, vectors, host cells containing the nucleic acids and methods for preparation and producing such proteins; Antibodies induced or generated by the use of said malaria vaccines or said nucleic acid molecules encoding said proteins and / or fusion proteins and the use of such antibodies or recombinant derivatives for passive immunotherapy.

The present invention features immunogenic compositions based on pre-fertilization or post-fertilization antigens expressed in the circulating gametocytes in the peripheral blood of infected persons or on the malaria parastes' stages of develop-ment in the mosquito midgut including extracellular male and female gametes, fertilized zygote and ookinete. The invention also features methods to prevent the transmission of malaria using the immunogenic compositions of the invention.

The present invention discloses influenza virus hemagglutinin protein and peptide of malaria antigen of Plasmodium falciparum (Plasmodium falciparum), antibody specific to said peptide, influenza vaccine, malaria vaccine and immunity stimulating patients to produce anti-influenza virus or malaria antibody method of response. The invention also discloses methods for formulating vaccines against influenza viruses. The invention discloses an isolated peptide of Bacillus anthracis (Bacillus anthracis) anthrax toxin lethal factor protein pX01-107, an antibody specific to the peptide and an antibody that stimulates patients to produce anti-Bacillus anthracis anthrax toxin lethal factor protein pX01-107 method of the immune response. The present invention also discloses isolated peptides of the smallpox virus surface antigen S precursor protein, antibodies specific to said peptides and methods of stimulating an immune response in a patient to produce antibodies against the smallpox virus surface antigen S precursor protein.

The invention relates to fusion proteins which comprise at least one antigenic amino acid sequence fused to a carrier heterologous protein sequence, wherein the antigenic sequence comprises an epitopic sequence of a Plasmodium protein and the carrier heterologous protein sequence is a sequence that is immunogenic in humans. The proteins are useful as anti-malaria vaccines.

The present invention refers to a recombinant malaria vaccine and a method for its manufacture.

The present invention provides a polypeptide and a malaria vaccine comprising the polypeptide, the polypeptide comprising any of the following amino acid sequences: (a) an amino acid sequence represented by SEQ ID NO. 4 or SEQ ID NO. 8; (b) an amino acid sequence represented by SEQ ID NO. 4 or SEQ ID NO. 8, in which 1-10, preferably 1-5, and more preferably 1-3 amino acids have been substituted, deleted, added or inserted; and (c) an amino acid sequence having at least 95%, preferably at least 97%, and more preferably at least 99% sequence identity with SEQ ID NO. 4 or SEQ ID NO. 8.

The invention relates immunogenic polypeptides and epitopes from Plasmodium falciparum protein AMA 1. The epitopes contain HLA class I binding motifs and stimulate an anti-malaria CD8+ T-cell response. The polypeptides can be incorporated into immunogenic formulations against malaria. Additionally, the antigens are useful for facilitating evaluation of immunogenicity of candidate malaria vaccines.

The present invention relates to a method for recombinant production of a fusion protein comprising multiple malaria antigens for inducing immune responses comprising a combination of antibodies. In particular, the fusion proteins of the present invention comprise fragments of both Pfs230 and Pfs48 / 45 to lower the required threshold of functional antibodies and to reduce the risk of escape mutations. Thus, the fusion proteins of the present invention are suitable for use in a multivalent malaria vaccine.

The invention discloses an antibody for inhibiting the growth of Plasmodium cynomolgus monkey in vitro, belonging to the fields of parasitology and immunology. The antibody is prepared from PvMSP8+1 recombinant protein, and the PvMSP8+1 recombinant protein is a fusion protein composed of Plasmodium vivax merozoite surface protein 8 (PvMSP8) and the C-terminal of 1 (PvMSP1‑19). In the in vitro growth inhibition assay, the PvMSP8+1 antibody showed a superior inhibitory effect than the PvMSP8 and PvMSP1‑19 single antigen antibodies. This provides a certain scientific basis for the development of multi-antigen malaria vaccines, and has broad application prospects.

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.

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.

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.

The invention discloses an antibody for inhibiting growth of Plasmodium cynomolgi in vitro, and belongs to the field of parasitics and immunology. The antibody is prepared from a PvMSP8 + 1 recombinant protein, and the PvMSP8 + 1 recombinant protein is a fusion protein composed of Plasmodium vivax merozoite surface protein 8 (PvMSP8) and the C terminal (PvMSP1-19) of 1. In an in-vitro growth inhibition test, the PvMSP8 + 1 antibody shows an inhibition effect superior to that of PvMSP8 and PvMSP1-19 monoantigen antibody. A certain scientific basis is provided for people to develop the multi-antigen malaria vaccine, and the antibody has a wide application prospect.