Abstract: This invention provides an isolated nucleic acid which comprises a nucleotide segment having a sequence encoding a viral envelope protein comprising a viral surface protein and a corresponding viral transmembrane protein wherein the viral envelope protein contains one or more mutations in amino acid sequence that enhance the stability of the complex formed between the viral surface protein and transmembrane protein. This invention also provides a viral envelope protein comprising a viral surface protein and a corresponding viral transmembrane protein wherein the viral envelope protein contains one or more mutations in amino acid sequence that enhance the stability of the complex formed between the viral surface protein and transmembrane protein. This invention further provides methods of treating HIV-1 infection.

Abstract: This invention is directed toward a peptide corresponding to an immunologically important viral epitope. Specifically, the peptide corresponds to an immunodominant epitope identified in the envelope region of the human immunodeficiency virus type 1 (HIV-1). This peptide has the following amino acid sequence: NH2-Asn-Asn-Thr-Arg-Arg-Gly-Ile-His-Met-Gly-Trp-Gly-Arg-Thr-Phe-Tyr-Ala-Thr-Gly-Glu-Ile-Ile-Gly-CO2H (SEQ ID NO:17). The invention also relates to the use of this peptide, particularly when biotinylated in the form of complexes of streptavidin-biotinylated peptides or of avidin-biotinylated peptides, for the in vitro determination of HIV-1-specific antibodies.

Abstract: Oligonucleotide sequences encoding gp120 polypeptides from breakthrough isolates of vaccine trials using MN-rgp120 and the encoded gp120 polypeptides are provided. Use of the gp120 polypeptides from one or more of the isolates in a subunit vaccine, usually together with MN-rgp120, can provide protection against HIV strains that are sufficiently different from the vaccine strain (e.g.; MN-rgp120) that the vaccine does not confer protection against those strains. Antibodies induced by the polypeptides are also provided.

Abstract: The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Abstract: This invention is in the field of lymphadenopathy virus. This invention relates to a diagnostic means and method to detect the presence of DNA, RNA or antibodies of the lymphadenopathy retrovirus associated with the acquired immune deficiency syndrome or of the lymphadenopathy syndrome by the use of DNA fragments or the peptides encoded by said DNA fragments. The invention further relates to the DNA fragments, vectors comprising them and the proteins expressed.

Abstract: The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralize a wide spectrum of HIV primary isolates. The invention also relates to a method of inducing anti-HIV antibodies using same.

Abstract: The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein, which peptides are lethal to malignant or transformed cells when fused to a membrane-penetrating leader sequence. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide fused at its carboxy terminal end to a membrane-penetrating leader sequence are also provided.

Abstract: The invention concerns a vaccine composition comprising at least an antigen, a cationic lipid and an immunostimulatory oligonucleotide. Said vaccine composition is particularly designed to induce an immune response of the Th1 type and a cytotoxic T response when administered by parenteral delivery, and to induce a Th2 type immune response when delivered through the mucous system. Said composition is of particular interest when the cationic lipid is DC chol.

Abstract: A replication-competent recombinant Sabin type 1 poliovirus vector containing a sequence coding for multiple cloning site and 3C-protease cleavage site is provided. This vector makes it easy to introduce various vaccine genes from infectious viruses to the Sabin 1 poliovirus, and facilitates to produce chimeric Sabin 1 polioviruses that are expected to be powerful oral mucosal vaccines against several infectious viral diseases.

Abstract: The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

Abstract: The present invention relates to prophylactic and therapeutic acquired immunodeficiency syndrome vaccines. In particular, the present invention provides methods and compositions utilizing recombinant HIV-1, HIV-2 and/or SIV genes or gene products in safe vaccination approaches.

Abstract: A virus neutralizing level of antibodies to a primary HIV isolate is generated in a host by a prime-boost administration of antigents. The primary antigen is a DNA molecule encoding an envelop glycoprotein of a primary isolate of HIV-1 while the boosting antigen is either a non-infectious, non-replicating HIV-like particle having the envelope glycoprotein of a primary isolate of HIV-1 or an attenuated viral vector expressing an envelope glycoprotein of a primary isolate of HIV-1.

Abstract: This invention provides a therapeutic agent capable of specifically forming a complex with human immunodeficiency virus envelope glycoprotein which comprises a polypeptide. In one embodiment of the invention, the amino acid sequence of the polypeptide comprises the amino acid sequence shown in FIG. 6 from about +1 to about +185 fused to the amino acid sequence from about +353 to about +371. In another embodiment of the invention, the amino acid sequence of the polypeptide comprises the amino acid sequence shown in FIG. 6 from about +1 to about +106 fused to the amino acid sequence from about +353 to about +371. In yet a further embodiment of the invention, the amino acid sequence of the polypeptide comprises the amino acid sequence shown in FIG. 6 from about +1 to about +185.

Abstract: The invention provides an immunogenic composition comprising at least one antigen in association with microparticles, wherein the microparticles are in the same size range as viruses. In addition the invention also provides vaccine compositions and methods of eliciting immune responses in a subject.

Abstract: The present invention relates to a method for inducing antibodies neutralizing HIV primary isolates in a mammal, comprising administration of a pharmaceutical composition comprising a polypeptide represented by the formula N-L-C, in which:

Abstract: 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.

Abstract: The present invention provides a Tat protein wherein all the cysteine residues of the cysteine-rich domain have been replaced with another amino acid, preferably with serine, nucleic acids encoding it, and methods of using it to elicit a humoral and cellular immune responses in a mammal. The Tat protein of the invention is therefore useful, inter alia, for prophylactic and/or therapeutic anti-HIV use as well as raising anti-native Tat antibodies in mammals.

Abstract: An isolated ferritin fusion protein is provided in which ferritin is fused with a protein or peptide capable of being fused to ferritin without interfering with the polymeric self-assembly of the resulting fusion protein, and the protein may be of the endocapsid form when fused at the C terminus or an exocapsid form when fused at the N terminus. These fusion proteins may self-assemble into a variety of useful higher polymeric forms, e.g., capsid or other polymeric aggregate, and they are advantageous in that they are useful in a variety of applications, including human and veterinary vaccines and therapeutics, blood substitutes, image contrast agents, metal chelating agents, gelling agents, protein purification platforms, and therapeutic receptor-binding proteins.

Abstract: The present invention relates, generally, to a polyvalent immunogen and, more particularly, to a method of inducing neutralizing antibodies against HIV and to a polyvalent immunogen suitable for use in such a method.

Abstract: This invention is directed to antigen library immunization, which provides methods for obtaining antigens having improved properties for therapeutic and other uses. The methods are useful for obtaining improved antigens that can induce an immune response against pathogens, cancer, and other conditions, as well as antigens that are effective in modulating allergy, inflammatory and autoimmune diseases.

Abstract: The invention concerns the use of a protein derived from cancer cells, virus-infected cells or immune-defence cells or a fragment of said protein, characterized in that said protein is initially an immunosuppressive and/or angiogenic protein with local activity and said properties are inactivated by at least 70%, through a physical and/or chemical treatment, by genetic recombination or by adjuvant conditioning, said treatment preserving its property of being identified by antibodies directed afainst said protein, and preserving sufficient immunogenic properties for generating antibodies neutralizing or blocking said native protein, to obtain a medicine for use as local anti-immnumosuppression and/or anti-angiogenic agent as an anticancer agent. The invention also concerns the resulting immunogenic compounds, their preparation method and their uses.

Abstract: The invention provides compositions containing HIV epitopes, which are recognized by cytotoxic T lymphocytes (CTL). Such polypeptides are used in vaccines and immunotherapies. HIV-1 epitopes represent early targets in a naturally-occurring response against HIV-1 infection.

Abstract: The present invention is directed to vaccine compositions that can be used to protect cats against feline immunodeficiency virus. More particularly, the present invention relates to polynucleotide molecules that can be used as vaccine components against feline immunodeficiency virus.

Abstract: Anti-lentivirus vaccines and immunotherapeutics and methods for preparing and using same are disclosed. The vaccines and immunotherapeutics are produced using non-immunosuppressive lentivirus trans-activator of transcription (Tat) proteins. An associated in vitro ultra-sensitive macrophage Tat bioassay is disclosed for assessing the immunosuppressive qualities of the lentivirus Tat preparations of the present invention. Additionally, a related long-term T4 cell propagation system for characterizing lentivirus Tat is also disclosed. The present invention has additional utility in the treatment and prevention of AIDS.

Abstract: The invention relates to a new class of retroviruses, designated by HIV-2, of which samples have been deposited to the ECACC under numbers 87.01.1001 and 87.01.1002 and to the NCIB under numbers 12.398 and 12.399. It relates also to antigens capable to be obtained from this virus, particularly proteins p12, p16, p26 and gp140. These various antigens can be used for the diagnosis of the disease, especially by contacting these antigens with a serum of a patient submitted to the diagnosis. It relates to immunogenic compositions containing more particularly the glycoprotein gp140. Finally it concerns nucleotidic sequences, which can be used especially as hybridization probes, derived from the RNA of HIV-2.

Abstract: The invention is a general method for improving the performance of the DNA-based vaccines. The method utilizes a complex DNA-generated profile of antigens to extend the effects of DNA-based vaccines and to broaden the immune response. This broadened immune response in turn improves the protection of the recipient from divergent (but related) strains of a pathogen. In addition, it effectively improves the efficacy of DNA-based vaccines used for treatment of viral diseases, including acquired immunity disorder (AIDS). One embodiment, where the target viral pathogen is HIV (the causative agent for aids), the method identifies an orderly set of plasmids of related sequences that may be used to prime a broad and strong immune response to HLA-restricted viral antigens. This mixture of plasmids is thus capable of priming an appropriate immune response to reduce the viral burden in HIV infected patients or to protect uninfected patients from HIV infection.

Abstract: A variant of a LAV virus, designated LAVMAL and capable of causing AIDS. The cDNA and antigens of the LAVMAL virus can be used for the diagnosis of AIDS and pre-AIDS.

Abstract: This invention discloses diagnostic, preventative, and treatment therapies of AIDS involving determining whether a subject exhibits an HLA-Cw7-restricted CTL response. Some methods are directed to the use of HLA-Cw7 as a genetic marker for long-term non-progression and amenability to treatment therapies. Diagnostic methods include a method for predicting long term non-progression in an HIV-infected subject. Preventative and treatment methods encompass determining whether a subject exhibits or can exhibit an HLA-Cw7-restricted CTL response. They also encompass ways of eliciting such a response, if necessary. Furthermore, some of the methods involve administering one or more HIV polypeptides or peptides, or polynucleotides encoding them, as a treatment therapy to prevent the development of AIDS.

Abstract: The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralize a wide spectrum of HIV primary isolates. The invention also relates to a method of inducing anti-HIV antibodies using same.

Abstract: The invention features an immunogenic composition containing a frequently-recognized epitope of an HIV-1 accessory protein and methods of inducing an immune response using such an epitope. The epitope peptide contains an amino acid sequence of a functionally active domain or a structural domain of the accessory protein.

Abstract: Stable, helical, biologically active peptides, particularly stable, helical, biologically active C-peptides, which comprise all or a portion of an unstructured peptide (a peptide which is unstructured in solution) linked to a scaffold (or support) polypeptide. Such peptides are referred to herein as structured C-peptides. In particular embodiments, structured C-peptides of the present invention comprise all or a portion of a binding epitope of a C-peptide, such as all or a portion of a binding epitope of a peptide derived from the carboxy-terminal region of the HIV-1 gp41 envelope glycoprotein. The C-peptide can be, for example, C34 peptide of HIV-1 gp41.

Abstract: Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

Abstract: This invention relates to antiviral drug susceptibility and resistance tests to be used in identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and further relates to the means and methods of monitoring the clinical progression of HIV infection and its response to antiretroviral therapy, particularly nucleoside reverse transcriptase inhibitor therapy using phenotypic susceptibility assays or genotypic assays.

Abstract: Anti-lentivirus vaccines and immunotherapeutics and methods for preparing and using same are disclosed. The vaccines and immunotherapeutics are produced using non-immunosuppressive lentivirus trans-activator of transcription (Tat) proteins. An associated in vitro ultra-sensitive macrophage Tat bioassay is disclosed for assessing the immunosuppressive qualities of the lentivirus Tat preparations of the present invention. Additionally, a related long-term T4 cell propagation system for characterizing lentivirus Tat is also disclosed. The present invention has additional utility in the treatment and prevention of AIDS.

Abstract: A method for increasing immune responses of a human patient infected with HIV, involving contacting the T-cells, in vitro or in vivo, with an organic compound at a concentration effective to cause T-cell proliferation, but below an amount that causes detectable cytotoxicity.

Abstract: This invention relates to the fields of genetic engineering, virus replication and gene transfer. More specifically, this invention relates to polynucleotide construct, recombinant virus, transposon, and their vectors, wherein an ori derived from a DNA virus capable of replicating in vertebrate cells is inserted into the retrovirus, allowing the retrovirus following the reverse transcription to efficiently replicate as extrachromosomal or episomal DNA without the necessity of integration into the host cell chromosome. Additionally, this invention relates to polynucleotide construct, recombinant virus, transposon, and their vectors replicating episomally without aid of an ori and related elements. Also, this invention encompasses preventive, therapeutic, and diagnostic applications employing said constructs, viruses and vectors.

Abstract: The present invention provides for peptide conjugate compositions, methods of using the peptide conjugate compositions, and pharmaceutical compositions comprising the peptide conjugate compositions. The peptide conjugate compositions comprise peptides with amino acid sequences similar to the gp 120 principal neutralizing domain (PND) of HIV, gp41, and Nef (p27) of HIV and carriers which enhance immunogenicity. The peptide conjugate compositions of the present invention may comprise a multivalent cocktail of several different peptide conjugates. Also provided by present invention is a method for reducing the level of HIV titers in a mammal by administering to the mammal a peptide composition of the present invention in an amount effective to reduce the level of HIV titers. The peptide conjugate compositions of the present invention induce prolonged antibody response in serum, a high level of antibody in the mucosa, and the production of cytotoxic lymphocytes.

Abstract: The identification, separation, purification, and propagation of the HIV-1 virus is provided. Moreover, the preparation of antigens from HIV-1 is further provided. The identification of HIV-1 involves the purification of a virus sample from lymphocytes and contacting the sample with antibodies, which bind to HIV-1 viruses, is provided. The propagation of HIV-1 virus involves infecting uninfected T lymphocytes with the virus. Moreover, the preparation of antigens from HIV-1 involves the separation of protein components of a purified HIV-1 virus under denaturing conditions.

Abstract: The invention provides Cross-clade candidates that have “evolved” due to gene shuffling in vitro for inclusion of “cross-clade” characteristics. The invention also provides a method for identifying Cross-clade candidates that could be presented in the context of more than one HLA, due to the creation of promiscuous epitopes by gene shuffling.

Abstract: Recombinant human immunodeficiency virus antigens capable of immunologically identifying the presence of early anti-HIV antibodies are stably expressed in a number of cell lines. These antigens have several clinically important applications as non-hazardous tools in the detection of human immunodeficiency virus exposure/infection, and in screening methods for HIV infection in idiopathic chronic lymphopenia (ICL). These techniques are improved over existing immunologically based and PCR based detection methods, as they provide for the detection of infection/exposure in samples determined to be negative by conventional forms of these types of assays that do not detect anti-HIV gp16O antibodies that react to conformational epitopes of HIV. The invention finds particular application in the detection of human immunodeficiency virus exposure/infection in infants.

Abstract: We have developed DNA and viral vectors that can be used, alone or in combination, as a vaccine against one HIV lade, subtype, or recombinant form of HIV or against multiple HIV clades, subtypes, or recombinant forms. Moreover, the vectors can encode a variety of antigens, which may be obtained from one clade or from two or more different clades, and the antigens selected and/or the manner in which the vectors are formulated (e.g., mixed) can be manipulated to generate a protective immune response against a variety of clades (e.g., the clades to which a patient is most likely to be exposed; with the proportions of the components of the vaccine tailored to the extent of the patient's risk to a particular dade or clades).

Abstract: The present invention relates to peptides of one or more portions of the human chorionic gonadotropin &bgr;-chain as well as methods for treatment and prevention of diseases, including HIV infection, using human chorionic gonadotropin, employing the &bgr;-chain of human chorionic gonadotropin, peptides containing a sequence of one or more portions of the &bgr;-chain of human chorionic gonadotropin and derivatives and analogues thereof. The invention further relates to fractions of sources and or preparations of human chorionic gonadotropin, such as fractions of human early pregnancy urine, which fractions have anti-HIV activity. The present invention further relates to pharmaceutical compositions for treating and/or preventing HIV infection.

Abstract: Novel immune modulating processes are provided in which the imunological state of a subject including mature subjects, mammals and humans, are down regulated in a selective manner, and as a subset in a dominant manner. The novel immunological state termed SIDR for selective immune down regulation is usefully applied to the immunological modulation or regulation of gene delivery components, artificially expressed genes, gene delivery systems and expression products of artificially introduced genes by such delivery systems, and infectious agents. SIDR is also useful when combined with other immune modulating treatments such as general immune suppression and anti-apoptosis. SIDR may also be used to selectively down regulate the immune response system of a subject to a wide variety of noncellular immunogenic components and to native antigens. Other processes for producing immune suppression by administering macromolecules or compounds to a subject so as to obtain or effect SIDR are also provided.

Abstract: The invention relates to a new class of retroviruses, designated by HIV-2, of which samples have been deposited to the ECACC under numbers 87.01.1001 and 87.01.1002 and to the NCIB under numbers 12.398 and 12.399.

Abstract: This invention provides a method of inhibiting an autoimmune response in an animal suffering from an autoimmune disease selected from the group consisting of psoriasis, Lyme disease and hyper IgE syndrome which comprises administering to the animal, in an amount effective to treat the autoimmune disease, an antibody that binds specifically to a protein specifically recognized by monoclonal antibody 5c8 produced by the hybridoma having ATCC Accession No. HB 10916.

Abstract: The present invention pertains to mutated, non-infectious HIV viral particles, vectors for production of such particles and vaccines employing such vectors. The non-infectious particles are obtained by introducing a number of inactivating mutations into a native viral genome. These mutations are designed so as to minimize the probability of genetic reversion to an infectious virus, while retaining the basic protein content and immunogenic properties of a wild-type virion. The altered viral genome expresses proteins that can assemble into non-infectious particles which contain immunogenic components of the virus, but which are unable to infect cells. The preferred mutations are introduced in at least one amino acid position of the NC protein in combination with at least one other mutation in an amino acid position of the RT protein or the In protein.

Abstract: A carbohydrate peptide conjugate comprising:

Abstract: The invention provides the use of a) an HIV Tat protein or polynucleotide; or b) an HIV Nef protein or polynucleotide; or c) an HIV Tat protein or polynucleotide linked to an HIV Nef protein or polynucleotide (Nef-Tat); and an HIV gpl20 protein or polynucleotide in the manufacture of a vaccine for the prophylactic or therapeutic immunisation of humans against HIV.

Abstract: The invention provides a polynucleotide comprising portions of the genomes of caprine arthritis-encephalitis virus and HIV-1, resulting in a chimeric retrovirus referred to as a “CHIV. ” The invention also provides a vaccine comprising a CHIV immunogen and a pharmaceutically acceptable carrier. A method of stimulating an immune response in an individual-against human immunodeficiency virus-1 infection by administering a therapeutically effective amount of a CHIV immunogen is also provided. The invention further provides a method of stimulating an immune response in vitro by contacting a lymphocyte with a therapeutically effective amount of a CHIV immunogen.

Abstract: The present invention relates to the efficient expression of HIV polypeptides in a variety of cell types, including, but not limited to, mammalian, insect, and plant cells. Synthetic expression cassettes encoding the HIV Gag-containing polypeptides are described, as are uses of the expression cassettes in applications including DNA immunization, generation of packaging cell lines, and production of Env-, tat- or Gag-containing proteins. The invention provides methods of producing Virus-Like Particles (VLPs), as well as, uses of the VLPs including, but not limited to, vehicles for the presentation of antigens and stimulation of immune response in subjects to whom the VLPs are administered.