Abstract: Improved anti-HIV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus sequences for HIV Subtype A Envelope protein, those having consensus sequences for HIV Subtype B Envelope protein, those having consensus sequences for HIV Subtype C Envelope protein, those having consensus sequences for HIV Subtype D Envelope protein, those having consensus sequences for HIV Subtype B consensus Nef-Rev protein, and those having consensus sequences form HIV Gag protein subtypes A, B, C and D. Improved anti-HPV immunogens and nucleic acid molecules that encode them; improved anti-HCV immunogens and nucleic acid molecules that encode them; improved hTERT immunogens and nucleic acid molecules that encode them; and improved anti-Influenza immunogens and nucleic acid molecules that encode them are disclosed as well methods of inducing an immune response in an individual against HIV, HPV, HCV, hTERT and Influenza are disclosed.

Abstract: Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.

Abstract: The present invention relates to an attenuated, recombinant viral vaccine against yellow fever which expresses heterologous sequences of a lentivirus and is used as an immunisation agent to induce an immune response to lentivirus.

Abstract: The disclosure relates to immunological compositions for vaccinating human beings against infection by the Human Immunodeficiency Virus (HIV).

Abstract: The invention provides a composition comprising four adenoviral vectors, each comprising a nucleic acid sequence encoding a clade A HIV Env protein, a clade B HIV Env protein, a clade C HIV Env protein, and a clade B HIV Gag-Pol fusion protein, respectively. The invention also provides a method of inducing an immune response against HIV-1 in an animal comprising administering the composition to the animal.

Abstract: Env-CD4 polypeptide complexes and hybrids that expose cryptic epitopes important in virus neutralization are disclosed. Methods of diagnosis, treatment and prevention using the polypeptides are also provided.

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.

Abstract: The immunogenicity of the influenza virus hemagglutinin (HA) molecule may be increased by substitutions of amino acids in the HA sequence. The substitution of specific HA residues, such as asparagine at position 223 of H5 HA, increase the sensitivity of the hemagglutinin inhibition (HI) assay by altering receptor specificity and/or antibody-antigen binding. HA molecules containing such substitutions will be useful in the development of diagnostic reference viruses and improved influenza vaccines.

Abstract: Disclosed is a method for treatment of HIV related diseases comprising targeting complexes between on the one hand the C5 domain of gp120 and on the other hand gp41 or the C2 domain of gp120. The complexes may be stabilised by administering compounds, such as antibodies, capable of directly interacting with and stabilising the complex, or by immunizing with C5 and gp41/C2 derived material so as to induce antibodies that bind to and stabilise the complex.

Abstract: Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.

Abstract: The present invention relates, in general, to an immunogenic composition (e.g., a vaccine) and, in particular, to a polyvalent immunogenic composition, such as a polyvalent HIV vaccine, and to methods of using same. The invention further relates to methods that use a genetic algorithm to create sets of polyvalent antigens suitable for use, for example, in vaccination strategies.

Abstract: The present invention relates to consensus nucleotide and protein sequences for HIV-1 Clade A antigens, and to nucleotide and protein sequences for Clade A antigens from circulating HIV-1 field isolates wherein the antigen sequences are closely related to the these consensus sequences. Advantageously, the present invention relates to HIV-1 Clade A transgenes that are derived from such sequences, and that encode either HIV-1 Clade A Gag, Pol (RT and Int), and Nef (collectively “GRIN”), HIV-1 Clade A Gag, RT, and Nef (collectively “GRN”), or HIV-1 Clade A Env. The invention also relates to vectors containing such transgenes, including adenovirus vectors containing such transgenes. The invention also relates to immunogenic compositions comprising the HIV-1 Clade A antigens, nucleotide sequences, vectors, or transgenes of the invention, and to methods of generating an immune response against HIV in a subject by administering an effective amount of such immunogenic compositions.

Abstract: A method for treating HIV infection is disclosed. The method comprises administering to a patient in need thereof a therapeutically effective amount of a fusion protein comprising: a) a Pseudomonas Exotoxin A (PE) peptide comprising a binding domain and a PE translocation domain, the PE peptide being devoid of cytotoxic domain III; b) optionally gag24, being fused to the PE peptide; c) a fragment of gp120 C1 domain, being fused to the PE peptide or fused to the gag24 if the gag24 is present; d) a fragment of gp 120 C5 domain, being fused to the fragment of gp120 C1 domain; e) a fragment of gp41 amino acid sequence, being fused to the fragment of gp 120 C5 domain, and f) optionally an endoplasmic reticulum retention sequence, being fused to the C-terminus of the fragment of gp41.

Abstract: An HIV-1 type (or subtype) O retrovirus protein, or a natural or synthetic polypeptide or peptide including at least a part of said protein, which is capable of being recognized by antibodies isolated from a serum resulting from infection by an HIV-1 type O VAU strain or an HIV-1 type (or subtype) O DUR strain.

Abstract: The invention provides methods, compositions and kits for treating and or preventing an HIV infection. For example, HIV envelope-like polypeptides (wild-type HIV polypeptides and mimotopes) may be administered to an individual so as to induce a protective immune response to HIV. Alternatively, antibodies directed to the HIV envelope-like polypeptides may be administered to an individual to treat or prevent an HIV infection and/or one or more symptoms associated with the infection (e.g., AIDS).

Abstract: The present invention relates, in general, to human immunodeficiency virus (HIV), and, in particular, to a method of inducing neutralizing antibodies to HIV and to compounds and compositions suitable for use in such a method.

Abstract: Provided are peptide vaccines including the signal peptide domain of selected target antigens of intracellular pathogens. The peptide vaccines of the invention contain multiple class II and class I-restricted epitopes and are recognized and presented by the majority of the vaccinated human population. Further provided, in particular, are anti tuberculosis vaccines. Also further provided are compositions including the vaccines as well as their use to treat or prevent infection.

Abstract: Drug delivery compositions and methods of delivering compounds into a cell or into an individual are disclosed. Vaccines and methods of immunizing individuals are disclosed. Compositions for drug delivery including gene therapy and methods of treating individuals using such compositions are disclosed.

Abstract: The present invention relates to protein-protein interactions involved in AIDS. More specifically, the present invention relates to complexes of polypeptides or polynucleotides encoding the polypeptides, fragments of the polypeptides, antibodies to the complexes, Selected Interacting Domains (SID®) which are identified due to the protein-protein interactions, methods for screening drugs for agents which modulate the interaction of proteins and pharmaceutical compositions that are capable of modulating the protein-protein interactions.

Abstract: The present invention refers to Tat as the active principle for a prophylactic and/or therapeutic vaccine against HIV infection, the progression towards AIDS and the development of tumors and other syndromes and symptoms in subjects infected by HIV. Tat is in biologically active form either as recombinant protein or peptide or as DNA. More particularly, the invention refers to a vaccine based on HIV-1 Tat as immunogen, inoculated as DNA and/or recombinant protein or as peptides, alone or in combination with other genes or viral gene products (Nef, Rev, Gag) or parts thereof, or in combination with various immuno-modulant cytokines (IL-12, IL-15) or with the gene coding for an immuno-modulant cytokine or part thereof. Tat, Nef, Rev, Gag and the immuno-modulant cytokines are administrated both as a mixture of recombinant proteins, peptides or fusion proteins (Tat/Nef, Tat/Rev, Tat/Gag, Tat/IL-12, Tat/IL-15) or as plasmid DNA.

Abstract: Provided herein are small molecule CD4 mimetics effective to bind to HIV Env proteins. A CD4 mimetic of the invention, when bound to an Env protein, is effective to induce a conformational change in the Env protein such that cyptic epitopes on the Env protein are exposed. Also provided herein are related methods of identifying and using such small molecule CD4 mimetics, for example, to elicit an immune response in a subject upon administration.

Abstract: The present invention relates in general, to a formulation suitable for use in inducing anti-HIV-1 antibodies, and, in particular, to a formulation comprising Toll Like Receptor (TLR) agonists with HIV-1 gp41 membrane proximal external region (MPER) peptide-liposome conjugates for induction of broadly reactive anti-HIV-1 antibodies. The invention also relates to methods of inducing neutralizing anti-HIV-1 antibodies using such formulations.

Abstract: The present invention is directed to nucleic acid molecules encoding attenuated, non-functional virion infectivity factor (vif) proteins. The nucleic acid molecules of the invention are inserted into recombinant expression vectors and administered to mammals in order to induce a cellular and humoral immune response to the encoded protein product.

Abstract: The subject invention provides novel soluble PD-1 (sPD-1) proteins, nucleic acids, and fusion constructs thereof, for enhancing humoral and cell-mediated immunity of a subject. Also provided are therapeutic compositions comprising the sPD-1 proteins, nucleic acids, and fusion constructs of the subject invention. In a preferred embodiment, the therapeutic composition is formulated as a vaccine composition. Advantageously, the sPD-1 proteins, nucleic acids, and therapeutic compositions provide protective immunity against pathogenic infection including HIV infection. In additon, the subject invention can be used in the prevention and/or treatment of tumor or cancer.

Abstract: The present invention relates, in general, to an immunogenic composition (e.g., a vaccine) and, in particular, to a polyvalent immunogenic composition, such as a polyvalent HIV vaccine, and to methods of using same. The invention further relates to methods that use a genetic algorithm to create sets of polyvalent antigens suitable for use, for example, in vaccination strategies.

Abstract: Plants are engineered to express HIV related surface protein genes. The plants can be used as a source of the protein for a variety of purposes. Plant tissue can be orally administered to animals to elicit an immune response or provide protection from viral infection. The protein can be extracted and delivered to animals. Plant produced proteins can also provide a less expensive and more readily available source of the protein as reagents or in other experimentation involving HIV and SIV proteins.

Abstract: A Tat-based vaccine composition comprising at least one antigen coupled to at least one immunostimulatory lentivirus trans-activator of transcription (Tat) molecule wherein the antigen is a cancer antigen an infectious disease antigen or a fragment thereof and methods to treat disease by administering the Tat-based vaccine composition. An additional Tat-based vaccine composition comprising immunostimulatory lentivirus Tat is provided.

Abstract: Provided are immunogenic compositions based on the highly conserved, core CD4 binding site of the gp120 protein of the human immunodeficiency virus. One embodiment includes an antigenic conjugate of an electophilic derivative of HIV gp120 peptide 416-433, designated E-416-433, covalently linked to an immunogenic carrier protein. The compositions are effective in stimulating the production of HIV neutralizing antibodies in mammals. Provided also are related methods of immunization, methods of antibody production and antibodies obtained using the methods of the invention.

Abstract: The invention relates to a method of preventing or treating acquired immunodeficiency syndrome (AIDS) in a patient, wherein the patient is administered with a Tat protein comprising amino acid sequence SEQ ID NO: 1 or 2, or a variant thereof capable of stimulating an immune response against Tat proteins.

Abstract: A nucleic acid is provided which encodes a human TRIM-cyclophilin A fusion sequence encoding a human TRIM-CypA fusion protein which is active as an anti-viral agent, and in particular, as an anti-HIV-1 agent. Also provided is a nucleic acid encoding a polypeptide having both TRIM activity and cyclophilin activity. Also provided is an isolated polynucleotide encoding a human TRIM-CypA fusion protein, or variants thereof retaining the TRIM and cyclophilin A activities. Also provided are compositions thereof, antibodies that specifically bind thereto, and vectors and host cells comprising the nucleic acid or polypeptide. In addition, methods are provided for treating or preventing viral infection, or reducing viral load in a subject comprising administering the nucleic acid, polypeptide, vector, or composition to the subject in an amount effective to treat or prevent the viral infection.

Abstract: The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

Abstract: The present invention provides compositions and methods for the treatment and prevention of immune disorders.

Abstract: This invention relates to novel peptide immunogens that generate an immune response in mammals against HIV gp41, to pharmaceutical compositions that comprise such immunogens, and to methods of treating Immunodeficiency disease, especially HIV infection and AIDS, that employ such pharmaceutical compositions.

Abstract: The invention relates to fusion proteins comprising the amino acid sequence of at least three HIV proteins selected from Vif, Vpr, Vpu, Rev, and Tat or derivatives of the amino acid sequence of one or more of said proteins, wherein the fusion protein is not processed to individual HIV proteins having the natural N and C termini. The invention further concerns nucleic acids encoding said proteins, vectors comprising said nucleic acids, and methods for producing said proteins. The fusion protein, nucleic acids and vectors are usable as vaccines for the at least partial prophylaxis against HIV infections.

Abstract: The invention provides compositions, methods, and kits for the treatment or prevention of viral infections. The polyvalent (e.g., 2-valent) vaccines described herein incorporate computationally-optimized viral polypeptides that can increase the diversity or breadth and depth of cellular immune response in vaccinated subjects.

Abstract: The present invention relates, in general, to human immunodeficiency virus (HIV), and, in particular, to a method of inducing neutralizing antibodies to HIV and to compounds and compositions suitable for use in such a method.

Abstract: The invention relates to fusion proteins comprising the amino acid sequence of at least three HIV proteins selected from Vif, Vpr, Vpu, Rev, and Tat or derivatives of the amino acid sequence of one or more of said proteins, wherein the fusion protein is not processed to individual HIV proteins having the natural N and C termini. The invention further concerns nucleic acids encoding said proteins, vectors comprising said nucleic acids, and methods for producing said proteins. The fusion protein, nucleic acids and vectors are usable as vaccines for the at least partial prophylaxis against HIV infections.

Abstract: The invention relates to polynucleotides encoding modified immunogenic HIV-1 South African subtype C Env polypeptides. The modifications to the Env polypeptides include deletions of V1, V2 and the stem region. The expression cassettes may be used, for example, to express the encoded polypeptide. A recombinant expression system for use in a selected host cell comprising an expression cassette encoding for the modified HIV-1 Env polypeptide is also described.

Abstract: The present invention relates to the use of specific transporter cargo conjugate molecules for the transport of a substance of interest (cargo molecule) into white blood cells. Said transporter cargo conjugate molecules may be used for the treatment, prophylaxis, attenuation and/or amelioration of a disease and/or disorder involving white blood cells. The present invention also relates to manufacture of said transporter cargo conjugate molecules, to a method of transporting a substance of interest (cargo) into a white blood cell and to a white blood cell comprising said transporter cargo conjugate molecules or fragments thereof.

Abstract: The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

Abstract: The present invention relates to consensus nucleotide and protein sequences for HIV-1 Clade A antigens, and to nucleotide and protein sequences for Clade A antigens from circulating HIV-1 field isolates wherein the antigen sequences are closely related to the these consensus sequences. In a preferred embodiment, the present invention relates to HIV-1 Clade A transgenes that are derived from such sequences, and that encode either HIV-1 Clade A Gag, Pol (RT and Int), and Nef (referred to as “GRIN”), HIV-1 Clade A Gag, RT, and Nef (referred to as (“GRN”), or HIV-1 Clade A Env. The invention also relates to vectors containing such transgenes, including in preferred embodiment, adenovirus vectors containing such transgenes.

Abstract: The present invention relates to modified HIV-1 envelope proteins where one or more N-glycosylation sites have been deleted or modified, which produce a broadly cross reactive neutralizing response, their methods of use and antibodies which bind to these proteins. The invention also provides for nucleic acids, vectors, antibodies and pharmaceutical compositions that comprise said modified HIV-1 envelope proteins.

Abstract: Disclosed are antigens that include a target epitope that is defined by atomic coordinates of those amino acids of the antigen that contact an antibody of interest that specifically binds the antigen. The disclosed antigens have between about 10% and about 90% of surface exposed amino acid residues located exterior of the target epitope substituted as compared to a wild-type antigen and less than about 10% of the non-surface exposed amino acid residues substituted as compared to a wild-type antigen. Also disclosed are nucleic acids encoding these antigens and methods of producing these antigens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a human immunodeficiency type 1 (HIV-1) infection in a subject.

Abstract: Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.

Abstract: A method and conjugate for selectively killing antigen-activated T cells are disclosed. The conjugate is composed of a substantially uncharged antisense compound targeted against the human cFLIP protein, and a reverse TAT (rTAT) polypeptide coupled covalently to the antisense compound. The rTAT polypeptide is effective to produce selective uptake of the conjugate into antigen-activated T cells, relative to the uptake of the conjugate into non-activated T cells. The cFLIP antisense compound causes activation induced cell death (AICD) of activated lymphocytes. The method is useful in treating transplantation rejection and autoimmune conditions.

Abstract: The invention relates to nucleic acids (such as DNA immunization plasmids), encoding fusion proteins containing a destabilizing amino acid sequence attached to an amino acid sequence of interest, in which the immunogenicity of the amino acid sequence of interest is increased by the presence of the destabilizing amino acid sequence. The invention also relates to nucleic acids encoding secreted fusion proteins, such as those containing chemokines or cytokines, and an attached amino acid sequence of interest, in which the immunogenicity of the amino acid sequence of interest is increased as a result of being attached to the secretory sequence. The invention also relates methods of increasing the immunogenicity of the encoded proteins for use as vaccines or in gene therapy.

Abstract: The invention provides a recombinant multi-functional chimera of CVN and 12p1. Chimeras of CVN and 12p1 present a model for targeting gp120 at two discrete sites, by two different modes of inhibition and with increasing potency versus either component alone. A chimera of the invention combines the high affinity suppression of viral activity by CVN with the allosteric suppression of viral envelope binding to both CD4 and co-receptor by 12p1.

Abstract: Compounds, which inhibit the binding of gp120 to CD4 as well as 17b and methods for their use in inhibiting the HIV fusion process, are provided.

Abstract: The present invention provides isolated methylated Tat peptides; and compositions comprising the peptides. The present invention further provides isolated antibodies specific for a Lys-51-methylated Tat polypeptide. Also provided are methods of identifying agents that inhibit Lys-51 methylation of a Tat polypeptide. The present invention further provides methods of treating an immunodeficiency virus infection in a mammalian subject.

Abstract: This invention features polypeptides, variants thereof, and fragments thereof useful in eliciting an immune response (e.g., neutralizing antibodies) against abroad spectrum of HIV-I isolates. The polypeptides, variants, and fragments include a portion of the gp120 V2 domain of HIV-I. The polypeptides, variants, and fragments display an epitope that is recognized by at least one antibody which neutralizes at least one HIV-I primary isolate. This invention also features nucleic acid sequences encoding those polypeptides. In addition, the invention provides methods of screening for inhibitors of HIV-I entry into cells, as well as methods of treatment using the inhibitors.