Institut Pasteur

Vac-4-All Pte. Ltd.

Univiersite De Lausanne

Université De Lausanne

Ram Biotech Aps

Pierre Druilhe

Claudine Guerin-Marchand

Gordon Langsley

Hasnaq Bouharoun-Tayoun

Claude Oeuvray

Claudine Marchand

Odile Puijalon-Mercereau

Pierre Daubersies

Giampietro Corradin

Christian P Roussilhon

Ali Jafarshad

Morten Steen Hanefeld Dziegiel

Rasmus Lundquist

Leif Kofoed Nielsen

Anne-Charlotte Grüner

Karima Brahimi-Zeghidour

Christian Roussillhon

The present invention pertains to the protection against malaria. More particularly, the invention is based on the characterization of a novel liver and sporozoite-stageantigen, 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.

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The present application relates to a sub-region of aprotein, with improved vaccine potential, and to medical uses thereof, notably for treatment or diagnosis of malaria. The present invention notably provides unstructured or unfolded polypeptides deriving from the PFF0165c protein of3D7. The polypeptides of the invention have a high antigenicity, a high immunogenicity, have a high parasite-killing activity in the ADCI assay, and are strongly associated with clinical protection against malaria, and. The present invention thereby provides a vaccine for the palliative and/or curative treatment of malaria, which is specifically intended for infants, toddlers, children under the age of 5, pregnant women.

Sub-region of a plasmodium protein with improved vaccine potential, and medical uses thereof

The present invention relates to a recombinant human antibody comprising an antibodysequence specific for the MSP-3 antigen of. In particular, the invention relates to a recombinant human antibody which is specific for the MSP-3antigen. The invention further relates to nucleic acid encoding such antibodies and to uses of these antibodies, in particular in the treatment or prophylaxis of malaria.

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.. MSP3 determinants include targets of antibody-dependent cellular inhibition (ADCI) which is a protective mechanism againstmalaria. 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. Distinct patterns of antibody responses, by level and IgG subclass distribution, were observed to MSP3 peptides in inhabitants of a malaria-endemic area. Antibodies affinity purified toward each peptide differed in their functional capacity to mediate parasite killing in ADCI assays: 3 of 6 overlapping peptides had a major inhibitory effect on parasite growth. Passive transfer of anti-MSP3 antibodies in vivo in amouse model confirmed the functional properties of antibodies to these MSP3 determinants.

The invention provides novel preparations for a broad-spectrum antiplasmodial vaccine.

The invention concerns novelantigens 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.

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, 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 byand 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 ofin the hepatic cells.

The invention discloses isolated DNA sequences encoded by polypeptides characterized by the presence in their structure of one or more 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 ofin hepatic cells.

DNA sequences encoding peptide sequences specific for the hepatic stages of P. falciparum bearing epitopes capable of stimulating the T lymphocytes

The present invention relates, in part, to a purified polyclonal or monoclonal antibody which recognizes an epitope of a protein of 48,000 dalton, where the protein recognizes is a surface protein of a merozoite ofwhich has a peptide of SEQ ID NO:1 or a sequence wherein SEQ ID NO:1 has been modified by insertion, deletion or substitution and the sequence inhibits the binding of monoclonal antibody 245 tomerozoites, as well as fragments of the antibody; the present invention relates to composition and kits containing the same, as well as methods of using the same.

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.

Polypeptide molecules containing at least 10 consecutive amino acids of the amino acid sequence shown in, representing the LSA3 antigen, the following peptides being excluded: 

Malarial pre-erythrocytic stage polypeptide molecules

The present invention relates, in part, to a purified polyclonal or monoclonal antibody which recognizes an epitope of a protein of 48,000 dalton, where the protein recognizes is a surface protein of a merozoite ofwhich has a peptide of SEQ ID NO:1 or a sequence wherein SEQ ID NO:1 has been modified by insertion, deletion or substitution and the sequence inhibits the binding of inonoclonal antibody 245 tomerozoites, as well as fragments of the antibody; the present invention relates to composition and kits containing the same, as well as methods of using the same;

Plasmodium falciparum antigens inducing protective antibodies

A molecule, protein or peptide characterized in that it is recognized by cytophilic antibodies from individuals who are immune to infection by Plasmodia, and recognized by non-cytophilic antibodies from individuals who are vulnerable to infection by Plasmodiae. Said antibodies are capable of blocking the erythrocytic phase of the parasite by co-operating with accessory cells such as monocytes.

Growing community of inventors

Paris, France

Pierre Druilhe