Institut Pasteur

Centre National De La Recherche Scientifique

Institut National De La Recherche Scientifique

Other

Cnrs

Institute Pasteur

Institut Pasteur and Centre National De La Recherche Scientifique

Institut Pasteur and Centre Nationale De La Recherche Scientifique

Bernard Krust

Luc Montagnier

Ara G Hovanessian

Marie-Anne Rey

Anne G Laurent

Jean-Claude Chermann

Solange Chamaret

Anne G Laurent-Crawford

Pierre Sonigo

Marc Alizon

Simon Wain-Hobson

Francois Clavel

Stewart T Cole

Francoise Barre-Sinoussi

Jean-Paul Briand

Sylviane Muller

Cole Stewart

Olivier Danos

Francedillaois Clavel

Marie-Anne Rey-Cuillé

Elias Said

Fran&ccedil;ois Clavel

François Clavel

Josette Svab

Marie-Anne Rey Cuill&eacute;

Francedillaoise Barre-Sinoussi

Francedillaoise Rey

Marie-Anne Rey Cuille

Anne G Laurent Crawford

Fran&ccedil;oise Barre-Sinoussi

Luc Montangnier

Ara Hovanessian

Elias c/o Mr Said Nicolas Said

Françoise Barre-Sinoussi

The present invention relates to chimeric peptides having a caveolin-1 binding domain of an HIV-1 gp41 (CBD1) peptide or a variant of said CBD1, fused to a T helper epitope. In one aspect, the T epitope is from a peptide selected from the group consisting of a tetanus toxin, an HIV-1 Gag p24 and an HIV-1 Env-gp120. Compositions containing these chimeric peptides and pharmaceutical and immunogenic compositions as well as vaccines comprising these chimeric peptides also are part of the present invention. Methods to induce neutralizing antibodies against HIV-1 activity and uses of the chimeric peptides to treat or to prevent HIV-1 infection are also disclosed.

Synthetic peptides corresponding to overlapping neutralizing determinants in the CBD1 epitope induce broadly neutralizing antibodies

The present invention relates to peptides, referred to as CBD-1, CBD-2, CBM-1/TH-1, CBM-1/TH-2, CBM-2/TH-1, CBM-2/TH-2 and C-20 peptides, which are antigenic and elicit a protective immune response against HIV infection. Compositions, pharmaceutical compositions and vaccines comprising these antigenic peptides are also encompassed by the present invention, as well as neutralizing antibodies which inhibit infection of primary CD4+ T lymphocytes by various HIV isolates. Methods for diagnosis of HIV are also disclosed.

Synthetic peptide vaccines for HIV: the CBD epitope as an effective immunogen to elicit broadly neutralizing antibodies against HIV

Four glycoproteins of apparent molecular weights 300,000, 140,000, 125,000, and 36,000 (gp300, gp140, gp125, and gp36) are detectable in human immunodeficiency virus type 2 (HIV-2) infected cells. The gp125 and gp36 are the external and transmembrane components, respectively, of the envelope glycoproteins of HIV-2 mature virions. The gp300, which is a dimeric form of gp140, the precursor of HIV-2 envelope glycoprotein, is probably formed by a pH dependent fusion in the endoplasmic reticulum. Such a doublet is also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. On the other hand, the envelope glycoprotein precursor of HIV-1 does not form a dimer during its processing. Experiments carried out with various inhibitors of oligosaccharide trimming enzymes suggest that transient dimerization of the glycoprotein precursor is required for its efficient transport to the Golgi apparatus and for its processing. The gp300 is useful for detecting antibodies to HIV-2 antigens in human body fluids and for raising antibodies to gp300.

Immunogenic compositions comprising human immunodeficiency virus type 2 (HIV-2) glycosylated and unglycosylated envelope proteins and their methods of preparation

Immunological reagents obtained from multimeric forms of the HIV-2 and SIV envelope glycoproteins and their use in the detection of HIV-2, particularly, the HIV-2 proteins gp300, p200, p90, and p80, and gp300 of SIV.

Immunological reagents and diagnostic methods for the detection of human immunodeficiency virus type 2 utilizing multimeric forms of the envelope proteins GP300, P200, and P90/80

Characterization of the envelope transmembrane protein of human immunodeficiency virus type 2 (HIV-2) was carried out using murine polyclonal and monoclonal antibodies or patient sera specific for HIV-2 proteins. A 80-Mr glycoprotein (gp80) was produced in HIV-2 infected cells along with three other glycoproteins that were recently reported: the extracellular glycoprotein (gp125), the envelope glycoprotein precursor (gp140), and the transient dimeric form of gp140 (gp300). The gp125 and gp80 were detectable after the synthesis of gp140 and the formation of gp300. Among these four glycoproteins, only gp80 and gp125 were associated with HIV-2 virions. As the other glycoproteins, gp80 was recognized by all HIV-2 positive sera. A murine polyclonal antibody raised against the purified gp300 recognized all four glycoproteins. On the other hand, a monoclonal antibody raised against a synthetic polypeptide deduced from the sequence of the transmembrane glycoprotein of HIV-2, recognized gp140, gp300 and gp80; thus indicating that gp80 should be related to the transmembrane protein of the envelope. Dimerization of envelope glycoprotein precursor and the transmembrane glycoprotein was also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. Cimerization of the envelope precursors might be essential for the processing of these glycoproteins into the mature products, extracellular and transmembrane glycoproteins. Furthermore, the dimeric form of the transmembrane glycoproteins might be important for the optimal structure of the virus and thus for its infectivity.

Antibodies, that bind to HIV-2 transmembrane glycoprotein homodimer (gp 80)

The molecular cloning and characterization of a novel human retrovirus, designated lymphadenopathy-associated virus, or LAV, is disclosed. LAV was originally isolated from a patient with acquired immune deficiency syndrome (AIDS). A cloned LAV complementary DNA (cDNA) was used to screen a library of recombinant phages constructed from the genomic DNA of LAV-infected T lymphocytes. The nucleotide sequence of an insert obtained from the recombinant phage clone &lgr;J19 was ascertained through M13 shotgun cloning and the dideoxy chain termination sequencing method. The env coding region was identified and various hydrophilic peptides obtained therefrom. These peptides correspond to amino acids 551-577, 594-603, 621-630, 657-679, and 719-758 of the LAV envelope glycoprotein. These peptides should provide suitable diagnostic reagents for the detection LAV-specific antibodies and for the generation of LAV-specific immunological reagents.

Nucleic acids and peptides of human immunodeficiency virus type (HIV-1)

The invention relates to an isolated immune complex comprising a protein and an antibody that binds with said protein, wherein the protein is selected from the group consisting of gp80 of HIV-2 and gp65 of SIV, wherein said gp80 is a glycoprotein having an apparent molecular weight of 80 kDa, as determined by SDS-PAGE, and further wherein said gp65 is a glycoprotein having an apparent molecular weight of 65 kDa as determined by SDS-PAGE. Also provided are an immunogenic composition comprising an amount of gp80 protein of human immunodeficiency virus type 2 (HIV-2) sufficient to induce an immune response and a pharmaceutically acceptible carrier, and a composition comprising at least one antigen selected from the group consisting of gp80 protein of HIV-2 and gp65,.

Immunogenic compositions comprising dimeric forms of the human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus (SIV) envelope glycoproteins

Immunological reagents obtained from multimeric forms of the HIV-2 and SIV envelope glycoproteins and their use in the detection of HIV-2 are disclosed. Particularly, the HIV-2 proteins, gp300, p200, p90, and p80, and gp300 of SIV are described.

Immunological reagents and diagnostic methods for the detection of human immunodeficiency virus type 2 utilizing multimeric forms of the envelope proteins gp300, p200, and p90/80

This invention is directed to a composition comprising one or more human immunodeficiency virus type 2 (HIV-2) envelope proteins and a pharmaceutically acceptable carrier. The proteins of the claimed invention are gp300, p200 and p90/80 of HIV-2. The composition is useful for the diagnostic assay of HIV-2 and as an antigen for the production of antibodies, for example.

Immunogenic compositions comprising glycosylated and deglycosylated

This invention is directed to nucleic acids derived from the pol region of the genome of human immunodeficiency virus type 1 (HIV-1). The nucleic acids are useful as probes for the detection of HIV-1. More particularly, this invention is directed to nucleic acids encoding a pol region of HIV-1 extending from about nucleotide 1856 to about 1906 and extending from about nucleotide 2048 to about nucleotide 2797.

Nucleic acids and pepties of human immunodeficiency virus type-1 (HIV-1).

Characterization of the envelope transmembrane protein of human immunodeficiency virus type 2 (HIV-2) was carried out using murine polyclonal and monoclonal antibodies or patient sera specific for HIV-2 proteins. A 80-Mr glycoprotein (gp80) was produced in HIV-2 infected cells along with three other glycoproteins that were recently reported: the extracellular glycoprotein (gp125), the envelope glycoprotein precursor (gp140), and the transient dimeric form of gp140 (gp300). The gp125 and gp80 were detectable after the synthesis of gp140 and the formation of gp300. Among these four glycoproteins, only gp80 and gp125 were associated with HIV-2 virions. As the other glycoproteins, gp8O was recognized by all HIV-2 positive sera. A murine polyclonal antibody raised against the purified gp300 recognized all four glycoproteins. On the other hand, a monoclonal antibody raised against a synthetic polypeptide deduced from the sequence of the transmembrane glycoprotein of HIV-2, recognized gp140, gp300 and gp80; thus indicating that gp80 should be related to the transmembrane protein of the envelope. Dimerization of envelope glycoprotein precursor and the transmembrane glycoprotein was also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. Dimerization of the envelope precursors might be essential for the processing of these glycooroteins into the mature products, extracellular and transmembrane glycoproteins. Furthermore, the dimeric form of the transmembrane glycoproteins might be important for the optimal structure of the virus and thus for its infectivity.

HIV-2 transmembrane glycoprotein homodimer (gp 80)

A novel human retrovirus which is the aetiological agent of acquired immune deficiency syndrome (AIDS), designated lymphadenopathy-associated virus (LAV), was isolated from the lymph nodes of a patient suffering from generalized persistant lymphadenopathy. LAV displays a tropism for CD4.sup.+ lymphocytes, a Mg.sup.2+ -dependent reverse transcriptase (RT) activity, a density of 1.16-1.17 as determined by sucrose gradient centrifugation, a particle diameter of 139 nm, and a p25 antigen that is immunologically distinct from the HTLV-I/II p24 protein. Radioimmunoprecipitation analysis (RIPA) of .sup.35 S-cysteine-labeled viral or cellular lysates employing patient antisera resulted in the identification of a viral antigen having a molecular weight of 110 kDa. Endoglycosidase treatment of this antigen produces a protein with a molecular weight of 90 kDa. Methods are disclosed for the preparation of hybridomas producing LAV gp110-specific monoclonal antibodies (Mabs). Methods are also disclosed employing these MAbs in the purification of the LAV envelope glycoprotein, gp110.

Methods for the preparation of hybridomas producing

The invention relates to new purified antigens of the LAV virus. They have molecular weights of about 135,000 and 150,000 daltons. They are useful for the detection of LAV antibodies in human sera. They are produced by hybrid cell-lines resulting from the fusion of T4 lymphocytes and cells of the MOLT-4 cell line.

Hybrid cell line formed between T4 lymphocytes and tumoral lymphoid type

Character of the envelope transmembrane protein of human immunodeficiency virus type 2 (HIV-2) was carried out using murine polyclonal and monoclonal antibodies or patient sera specific for HIV-2 proteins. A 80-Mr glycoprotein (gp80) was produced in HIV-2 infected cells along with three other glycoproteins that were recently reported: the extracellular glycoprotein (gp125), the envelope glycoprotein precursor (gp140), and the transient dimeric form of gp140 (gp300). The gp125 and gp80 were detectable after the synthesis of gp140 and the formation of gp300. Among these four glycoproteins, only gp80 and gp125 were associated with HIV-2 virions. As the other glycoproteins, gp80 was recognized by all HIV-2 positive sera. A murine polyclonal antibody raised against the purified gp300 recognized all four glycoproteins. On the other hand, a monoclonal antibody raised against a synthetic polypeptide deduced from the sequence of the transmembrane glycoprotein of HIV-2, recognized gp140, gp300 and gp80; thus indicating that gp80 should be related to the transmembrane protein of the envelope. Dimerization of envelope glycoprotein precursor and the transmebrane glycoprotein was also observed in cells infected with simian immunodeficiency virus (SIV), a virus closely related to HIV-2. Dimerization of the envelope precursors might be essential for the processing of these glycoproteins into the mature products, extracellular and transmembrane glycoproteins. Furthermore, the dimeric form of the transmembrane glycoproteins might be important for the optimal structure of the virus and thus for its infectivity.

Growing community of inventors

Paris, France

Bernard Krust