Abstract: This application describes an antibody that specifically binds to a synthetic oligomer (e.g., an oligonucleotide or oligopeptide) having a organic protecting group covalently bound thereto, which antibody does not bind to that synthetic oligomer when the organic protecting group is not covalently bound thereto. Methods of making and using such antibodies are also disclosed, along with cells for making such antibodies and articles carrying immobilized oligomers that can be used in assay procedures with such antibodies.

Abstract: The invention provides a novel post-transcriptional regulatory element that can function as an RNA nucleo-cytoplasmic transport element. The invention also provides for an attenuated HIV-1 hybrid virus for use as a vaccine and a kit incorporating the hybrid virus. The kit also includes instructional material teaching the use of the vaccine, where the instructional material indicates that the vaccine is used for the prophylaxis or amelioration of HIV-1 infection in a mammal; that the vaccine is to be administered to a mammal in a therapeutically effective amount sufficient to express a viral protein; where the vaccine will not cause clinically significant CD4+ cell depletion; and, the expression of the viral protein elicits an immune response to the attenuated HIV-1 virus. The invention further provides for a method for screening for post-transcriptional RNA nucleo-cytoplasmic transport element (NCTE) binding proteins.

Abstract: The immune response to a DNA immunogen in a mammal can be enhanced by administration of a chemokine or a polynucleotide encoding the chemokine. This method can be used, for example, to immunize or vaccinate a mammal against an infectious disease or a tumor.

Abstract: This invention is the discovery of novel specific epitopes and antibodies associated with long term survival of HIV-1 infections. These epitopes and antibodies have use in preparing vaccines for preventing HIV-1 infection or for controlling progression to AIDS.

Abstract: Disclosed are pharmaceutical compositions and methods for preventing or treating a number of amyloid diseases, including Alzheimer's disesase, prion diseases, familial amyloid neuropathies and the like. The pharmaceutical compositions include immunologically reactive amounts of amyloid fibril components, particularly fibril-forming peptides or proteins. Also disclosed are therapeutic compositions and methods which use immune reagents that react with such fibril components.

Abstract: Disclosed are pharmaceutical compositions and methods for preventing or treating a number of amyloid diseases, including Alzheimer's disesase, prion diseases, familial amyloid neuropathies and the like. The pharmaceutical compositions include immunologically reactive amounts of amyloid fibril components, particularly fibril-forming peptides or proteins. Also disclosed are therapeutic compositions and methods which use immune reagents that react with such fibril components.

Abstract: Compositions and methods for synthesizing and detecting HIV-2 specific amplicons. Particularly described are oligonucleotides that are useful as hybridization probes, and amplification primers that facilitate detection of very low levels of HIV-2 nucleic acids.

Abstract: Immunologically active peptides which are derived from a novel immunodeficiency virus which has the designation MVP5180/91 are described. A diagnostic containing such a peptide and methods of detecting an antibody against a retrovirus that causes immune deficiency using such diagnostic composition are also described. A kit containing the immunologically active peptides is also described. An immunogen and method of immunizing a mammal against HIV infection using the immunologically active peptides is described. DNA encoding the peptides and methods of detecting nucleic acids encoding HIV viruses are also described.

Abstract: The present invention thus provides a polypeptide capable of forming a structure corresponding to or mimicking the intermediate of gp41 as well as its use in a vaccine for treating or preventing HIV infections.

Abstract: Novel antiviral combinations for the treatment or prevention of viral infections, in particular, HIV, are disclosed. This new antiviral therapy employs either DP-178 or DP-107, viral fusion inhibitors, in combination with at least one other antiviral therapeutic agent. The combinations of the invention are better than single therapies alone, and in certain cases are synergistic. The use of DP-178 or DP-107 is an ideal therapy to combine with another antiviral, given both the novel mechanism which this therapeutic blocks HIV transmission and the non-toxicity of the therapeutic.

Abstract: This invention describes novel charged molecules which specifically bind to the Hepreceptor, a regulatory site which I have discovered in human ezrin. My invention is that when peptides or other charged molecules bind to the Hepreceptor, medically useful immune responses are induced. These charged molecules can be administered orally and by other routes for the treatment of various infectious diseases and cancer. I have determined that the Hepreceptor (human ezrin 308-373) comprises of two adjacent alpha helical domains which are folded together at a hinge region (M339-M340) and stabilised by complimentary side chain charges of the primary amino acid sequence in the soluble cytoplasmic conformation of ezrin. I have determined that in the unfolded membrane associated conformation of ezrin, the Hepreceptor is pushed through the cell membrane and is exposed on the outer surface of the cell. Hepreceptor-Domain A (amino acid numbers 308-339 of human ezrin), comprises of the following 32 amino acid sequence.

Abstract: Isolated HIV-1 Group O env polypeptides obtained from the HIV-1 isolate HAM112 are claimed, as well as (a) antigen constructs comprising fusions of one or more of each of HIV-1 Group O env polypeptides and HIV-1 Group M env polypeptide and (b) further antigen constructs containing additional Group O sequences and especially the gp41 IDR of isolate HAM112. Also claimed are polynucleotide sequences encoding the above, expression vectors comprising the same, host cells transformed thereby, and immunoassay methods and kits utilizing the antigen constructs of the invention.

Abstract: Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Abstract: Pharmaceutical compositions comprising the HIV protein vpr or nucleic acid molecule encoding vpr are disclosed. Also disclosed are methods of treating patients suffering from diseases characterized by hyperproliferating undifferentiated cells such as cancer by administering such compositions. Methods of identifying compounds which have anti-HIV activity are disclosed, in particular, methods of identifying compounds which modulate the activity of vpr and of identifying compounds which inhibit vpr binding to the HIV protein gag.

Abstract: The invention provides for the methods of modulating an immune response in an individual by administration of a thione-forming disulfide (TFD). Immunomodulatory responses include, but are not limited to, increased natural killer cell activity, expansion of NK cell population, decreased B cell population, decreased antibody production, and increased mitogenic potential. Methods of modulating such immune responses and the uses of immunomodulation are provided herein.

Abstract: The present invention provides compositions, including immunogenic compositions, comprising acetylated Tat protein of an immunodeficiency virus. The present invention further provides antibodies that specifically bind an acetylated Tat polypeptide. The present invention further provides methods of inducing an immune response to an immunodeficiency virus Tat protein in an individual. The present invention further provides methods of inhibiting transcriptional activation of an immunodeficiency virus in a cell of an individual.

Abstract: The present invention relates to an adjuvant derived from human lymphocytes. The adjuvant can be used in combination with traditional vaccines or cancer immunotherapy, to enhance the response of the patient's immune system to the vaccine or other immunotherapeutic agent. The adjuvant is derived from the supernatant collected from cultured activated lymphocytes.

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: Dendritic cells and macrophages can process extracellular antigens for presentation by MHC-I molecules. HIV-1 epitopes derived from incoming virions are presented through the exogenous MHC-I pathway in primary human dendritic cells, and to a lower extent in macrophages, leading to cytotoxic T lymphocyte activation in the absence of viral protein neosynthesis. Exogenous antigen presentation required adequate virus-receptor interactions and fusion of viral and cellular membranes. These results provide new insights about how anti-HIV cytotoxic T lymphocytes can be activated and are useful for anti-HIV vaccine design.

Abstract: The present invention relates to a plasmid carrying simian immunodeficiency virus (SIV)-derived genes. Particularly, the present invention relates to the plasmid pSIV/GE which carrys gag, protease, env and rev gene, all derived from SIV, but not tat and nef gene and the plasmid pSIV/pol which carrys SIV-derived pol gene; the plasmid pHIV/GE and pHIV/pol that are substituted the SIV-derived genes in the plasmid pSIV/GE and pSIV/pol by human immunodeficiency virus (HIV)-derived corresponding genes; DNA vaccine containing the plasmid pSIV/GE and pSIV/pol; and DNA vaccine containing the plasmid pHIV/GE and pHIV/pol. The present invention offers AIDS DNA vaccines which successfully exert perfect medicinal efficacy on primates, giving a measure of success in developing effective AIDS DNA vaccines applicable to humans. The plasmid of the present invention can be effectively used for not only AIDS prevention by AIDS infection but also therapeutic agent for AIDS.

Abstract: Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Abstract: The present invention relates to novel monoclonal antibodies which may be used in the detection of Human Immunodeficiency Virus (HIV). These antibodies exhibit an unusually high degree of sensitivity, a remarkably broad range of specificity, and bind to novel shared, non-cross-reactive epitopes. In particular, the monoclonal antibodies of the present invention may be utilized to detect HIV-1 antigen and HIV-2 core antigen in a patient sample.

Abstract: This invention provides a synthetic peptide vaccine against HIV and AIDS comprised of a potent helper epitope covalently linked to an HIV minimal CTL epitope. The vaccine induces potent epitope-specific CTL responses following a single administration in aqueous solution. This response can be further boosted with repeated administrations.

Abstract: Disclosed are compositions and methods for preferentially binding hK2 over PSA.

Abstract: The present invention is directed to the induction and characterization of a humoral immune response targeting “entry-relevant” gp41 structures. In its broadest aspect, the present invention is directed to methods of raising a neutralizing antibody response to a broad spectrum of HIV strains and isolates. The present invention targets particular molecular conformations or structures that occur at the cell surface of HIV during viral entry into host cells. Such a humoral response can be generated in vivo as a prophylactic measure in individuals to reduce or inhibit the ability of HIV to infect uninfected cells in the individual's body. Such a response can also be employed to raise antibodies against “entry relevant” gp41 structures. These antibodies can be employed for therapeutic uses, and as tools for further illuminating the mechanism of HIV cell entry.

Abstract: A method for the rational design and preparation of vaccines based on HIV envelope polypeptides is described. In one embodiment, the method for making an HIV gp120 subunit vaccine for a geographic region comprises determining neutralizing epitopes in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region and selecting an HIV strain having gp120 a neutralizing epitope in the V2 or C4 domain which is common among isolates in the geographic region. In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 are determined. At least two HIV isolates having different neutralizing epitopes in the V2, V3, or C4 domain are selected and used.to make the vaccine. The invention also provides a multivalent HIV gp120 subunit vaccine.

Abstract: The invention relates to a recombinant NS gene of an influenza A virus comprising a functional RNA binding domain and a gene sequence modification after nucleotide position 400 of the NS1 gene segment, counted on the basis of influenza A/PR/8/34 Virus, wherein the modification bars transcription of the remaining portion of the NS1 gene segment. It further relates to embodiments, wherein the modification comprises deletions, insertions, or a shift of the open reading frame, and particularly to constructs comprising an insertion of an autocleavage site 2A, the nef gene from HIV-1 or the sequence encoding the ELDKWA-epitope of gp4l of HIV-1. The invention also relates to influenza virus transfectants that contain the modified NS gene and have an IFN inducing phenotype but which may or may not be sensitive towards IFN. The invention also relates to vaccines comprising such a chimeric virus.

Abstract: Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV is disclosed. The compositions and methods described herein are for the use of a DNA composition that encodes one or more different HIV envelope glycoproteins. The DNA composition can encode an HIV Gag protein. The DNAs encoding one or more HIV proteins are a combination of different nucleic acids, such as DNA plasmids, generated from primary isolate DNA of different HIV major group genetic clades and/or different proteins. HIV protein compositions for inducing an immune response against HIV are disclosed. Methods for using the protein compositions as boosts following administration of the DNA compositions are provided.

Abstract: Recombinant adenovirus and methods of administration to a host are provided for eliciting immune response of the host to various pathogens. In one aspect of the invention, a vaccination method is provided for enhancing immunity of the host to the pathogen through rotation of the serotypes of the recombinant adenoviruses administered to the host.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif, by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: Methods and compositions for treatment, diagnosis, and prevention of a virus comprise administering to a patient antibodies which react with regions of viral proteins and result in neutralization of infectivity and inactivation of functionally essential events in the life cycle of the virus. The antibodies recognize viral epitopes which fail to elicit an immune response in man when encountered through infection or naturally through the environment. In a preferred embodiment, the invention provides compositions and methods useful in the treatment and diagnosis of human immunodeficiency virus (HIV) infections.

Abstract: Materials and methods of use thereof are presented for the prophylactic treatment of HIV. Therapeutic compositions including regulated aptamer therapeutic compositions with specificity to components of HIV disease are presented with methods of administering these therapeutic compositions as vaccines against HIV infection.

Abstract: Materials and methods of use thereof are presented for the treatment or diagnosis of HIV. The materials are aptamers that bind to gp41, CCR5 or other HIV viral targets that are involved in the formation of the gp41 fusion-active intermediate.

Abstract: A method for the rational design and preparation of vaccines based on HIV envelope polypeptides is described. In one embodiment, the method for making an HIV gp120 subunit vaccine for a geographic region comprises determining neutralizing epitopes in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region and selecting an HIV strain having gp120 a neutralizing epitope in the V2 or C4 domain which is common among isolates in the geographic region. In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 are determined. At least two HIV isolates having different neutralizing epitopes in the V2, V3, or C4 domain are selected and used to make the vaccine. The invention also provides a multivalent HIV gp120 subunit vaccine.

Abstract: The present invention comprises novel and modified peptides capable of inducing a HIV-1 specific immune response without antagonizing the cytotoxic T-cell activity in order to achieve an effective prophylactic and therapeutic vaccine against HIV. The peptides are based on conserved regions of HIV gag p17 and p24 proteins. Antigens in free- or carrier-bound form comprising at least one of the said peptides, vaccine compositions containing at least one of the antigens, immunoassay kits and a method of detecting antibodies induced by HIV or HIV specific peptides using such antigens, are described.

Abstract: The invention relates to a mixture of peptides originating from a Nef protein and the applications thereof as a medicine (in immunogenic compositions which stimulate the production in vivo of anti-HIV T CD4+ lymphocytes and are therefore useful for vaccinating against AIDS) or as a reactive diagnosis agent for T lymphocytes particular to HIV, particularly to assess the immune status of HIV-positive patients or patients undergoing anti-retroviral therapy. Each of said peptides in the mixture is linked to at least three HLA-DR molecules encoded by the alleles selected from the group comprising alleles HLA DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301 and DRB1*1501 (molecules DR1, DR3, DR4, DR7, DR11, DR13 and DR15) and to at least one HLA-DR molecule encoded by the alleles selected from the group comprising alleles HLA DRB3*0101, DRB4*0101 and DRB5*0101 (B3, B4 and B5;), with a binding capacity of<1000 nM, said mixture of peptides linking all of the aforementioned alleles.

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 invention provides methods for induction of an antigen-specific, mucosal cytotoxic T lymphocyte response useful in preventing and treating infections with pathogens that gain entry via a mucosal surface.

Abstract: An immunogenic proteoliposome containing a transmembrane protein or oligomeric complexes containing such proteins, including viral envelope glycoproteins, in a lipid membrane around an elliptoid or spherical shape. The shape preferably also contains an attractant such as streptavidin or avidin and the lipid membrane contains a moiety that binds to the attractant such as biotin. The immunogenic transmembrane protein is bound to a ligand which is anchored in the shape. Methods for making the immunogenic proteoliposomes are provided uses of the proteoliposome are described, including their use as immunogens to elicit immune reaction, and their use in screening assays, including their use as antigens to screen antibody libraries, as well as for drug screening and the identification of ligands.

Abstract: Described herein are chimeric peptides comprising a soluble trimeric coiled-coil and all or a portion of the N-peptide region of HIV gp41. These molecules are stable, trimeric coiled-coils that inhibit HIV entry into cells, such as human cells. Such peptides can be further assessed to demonstrate their ability to serve as potent anti-HIV therapeutic molecules and thus, as therapeutic molecules or drugs.

Abstract: The present invention provides antiviral proteins, peptides and conjugates, as well as methods of obtaining these agents. The antiviral proteins, peptides and conjugates of the present invention can be used alone or in combination with other antiviral agents in compositions, such as pharmaceutical compositions, to inhibit the infectivity, replication and cytopathic effects of a virus, such as a retrovirus, in particular a human immunodeficiency virus, specifically HIV-1 or HIV-2, in the treatment or prevention of viral infection.

Abstract: The present invention provides a fusion protein construct (gp41HA) consisting of the ectodomain of the HIV-1IIIB envelope glycoprotein gp41 fused to a fragment of the influenza virus HA2 hemagglutinin protein. Immunization in-vivo via an intraperitoneal prime followed by intranasal or intragastric boosts with gp41HA induces high concentrations of serum IgG antibodies and fecal IgA antibodies that reacted with gp41 in HIV-1IIIB viral lysate and are cross-reactive with gp41 in HIV-1MN lysate. Follow up analyses by indirect immunofluorescence showed that both serum IgG and fecal IgA recognized human peripheral blood mononuclear cells infected with either syncytium-inducing (SI) or non-syncytium-inducing (NSI) North American HIV-1 field isolates, but not uninfected cells.

Abstract: The invention provides immunogenic compositions which enhance &bgr;-chemokine levels in a mammal. The immunogenic compositions contain an HIV antigen, an isolated nucleic acid molecule containing an immunostimulatory sequence (ISS) and an adjuvant. The HIV antigen can be a whole-killed HIV virus devoid of outer envelope protein gp120. Alternatively, the HIV antigen can be a whole-killed HIV virus, or a p24 antigen. Also provided are kits, the components of which, when combined, produce the immunogenic compositions of the invention. The invention also provides methods of making the immunogenic compositions, by combining an HIV antigen, an isolated nucleic acid molecule containing an immunostimulatory sequence (ISS) and an adjuvant.

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: 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: Provided are synthetic peptides comprising amino acid sequence from the HR1 region of HIV-1 gp41, and having one or more amino acid substitutions in a hydrophobic domain of the HR1 region of HIV-1 gp41. As a result of the one or more amino acid substitutions in the hydrophobic domain, synthetic peptide self-assembles into trimers in solution. Also provided are trimers resulting from self-association of synthetic peptide. Additionally provided are methods of using these compositions to inhibit transmission of HIV to a target cell, or to inhibit HIV fusion to a target cell, wherein the methods involve adding an effective amount of synthetic peptide (or trimer formed therefrom) to inhibit viral transmission or viral fusion, respectively.

Abstract: The present invention is directed to a vaccine and method of neutralizing antibodies against HIV infection. The vaccine comprises a complex of gp120 covalently bonded to a fragment of CD4 or a CD4 equivalent molecule.

Abstract: Biochemical and structural studies of fragments of the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein have demonstrated that the molecular contacts between alpha helices allow the formation of a trimeric coiled coil. By introducing cysteine residues into specific locations along these alpha helices, the normally labile HIV-1 gp160 envelope glycoprotein was converted into a stable disulfide-linked oligomer. Although proteolytic cleavage into gp120 and gp41 glycoproteins was largely blocked, the disulfide-linked oligomer was efficiently transported to the cell surface and was recognized by a series of conformationally dependent antibodies. The pattern of hetero-oligomer formation between this construct and an analogous construct lacking portions of the gp120 variable loops and of the gp41 cytoplasmic tail demonstrates that these oligomers are trimers.

Abstract: Human immunodeficiency virus (HIV) is the primary etiologic agent for the acquired immune deficiency syndrome (AIDS). HIV exhibits considerable genotypic and phenotypic variability as manifested by different replicative kinetics, susceptibility to serum neutralization, antiviral drug resistance, cytopathic effects, and host-cell range specificity. Infection by HIV leads to progressive deterioration of cell-mediated immune responses making infected patients susceptible to a variety of opportunistic infections, such as pneumocystis carinii pneumonia (PCP), as well as, to the development of tumors such as Kaposi's sarcoma (KS). While the use of live-attenuated viruses to treat HIV infection has been proposed, to date researchers have been unable to demonstrate their efficacy in a clinical setting.

Abstract: The present invention is based, in part, on the discovery that a modified version of Peptide G (Asn Gly Gln Glu Glu Lys Ala Gly Val Val Ser Thr Gly Leu Ile—SEQ ID NO:2) obtained by replacing Asn with Asp to form Peptide G′ (Asp Gly Gln Glu Glu Lys Ala Gly Val Val Ser Thr Gly Leu Ile—SEQ ID NO: 1) overcomes the long range stabilization problem of the peptide conjugates and, quite surprisingly, also enhances the immune response, particularly the CD4 related (cell mediated) response, of conjugated peptides (L.E.A.P.S. constructs) as previously described.