Abstract: An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF.

Abstract: An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF.

Abstract: An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF.

Abstract: An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF.

Abstract: An immunogenic composition comprises a peptide that induces in vivo TNF monomer-specific antibodies that bind an epitope of dissociated monomers of human TNF, the epitope being located wholly or partially within a TNF monomer-monomer interface region. Antibodies induced in vivo by this composition disrupt assembly or prevent re-assembly of the TNF monomers into bioactive trimeric human sTNF. The composition can comprise an additional peptide that induces in vivo TNF monomer-specific antibodies that bind another epitope of dissociated monomers of human TNF. Methods of making these immunogenic compositions are also described. Methods for treating a subject having a disease mediated by human TNF comprise administering a described immunogenic compositions which induces antibodies in a treated subject that disrupt or reduce the in vivo assembly or reassembly of dissociated monomers of TNF into bioactive trimeric human sTNF.

Abstract: An isolated or synthetic antibody or ligand is provided that specifically binds to an epitope of a dissociated monomer of human TNF. Such binding disrupts assembly of the monomer into bioactive trimeric human sTNF. A pharmaceutical composition contains one or more antibodies or ligands: (a) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence PSDKPVAH or PSDKPVAHV, amino acids 8-15 or 8-16 of SEQ ID NO: 1; and (b) an antibody or ligand that specifically binds the TNF monomer-specific epitope having the sequence EPIYLGGVF, amino acids 116 to 124 of SEQ ID NO: 1. A combination of antibodies or ligands that bind or are reactive with (a) and/or (b) are useful in methods for treating a subject having a disease (e.g., rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis, atherosclerosis, metabolic syndrome, Alzheimer's Disease, HIV, Type II diabetes) mediated by human TNF.

Abstract: A self-adjuvanting immunogenic composition comprising multiple immunogens, each immunogen comprising a lipopeptide cap, a universal T helper sequence and an immunodominant HIV-1 Tat B cell epitope. The immunogen also comprises one or more linker sequences and/or polar charged amino acid sequences. The HIV-1 Tat B cell epitope of each immunogen has an amino acid sequence of V-D-P-Xaa7-L-Xaa9-P-W-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-amide SEQ ID NO: 1, in which the amino acid positions at Xaa7, Xaa9 and Xaa12 are selected from specific amino acid residues choices and in which the amino acid positions at Xaa13-Xaa16 may be absent or specific amino acid residue choices. The lipopeptide is a dipalmitoyl-S-glyceryl-cysteine or a tripalmitoyl-S-glyceryl cysteine or N-acetyl (dipalmitoyl-S-glyceryl cysteine), each with an optional neutral amino acid linker.

Abstract: A self-adjuvanting immunogenic composition comprising multiple immunogens, each immunogen comprising a lipopeptide cap, a universal T helper sequence and an immunodominant HIV-1 Tat B cell epitope. The immunogen also comprises one or more linker sequences and/or polar charged amino acid sequences. The HIV-1 Tat B cell epitope of each immunogen has an amino acid sequence of V-D-P-Xaa7-L-Xaa9-P-W-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-amide SEQ ID NO: 1, in which the amino acid positions at Xaa7, Xaa9 and Xaa12 are selected from specific amino acid residues choices and in which the amino acid positions at Xaa13-Xaa16 may be absent or specific amino acid residue choices. The lipopeptide is a dipalmitoyl-S-glyceryl-cysteine or a tripalmitoyl-S-glyceryl cysteine or N-acetyl (dipalmitoyl-S-glyceryl cysteine), each with an optional neutral amino acid linker.

Abstract: A single isolated antibody or antibody fragment thereof binds to multiple variant sequences within an epitope of HIV-1 Tat protein displayed in multiple strains and subtypes of HIV-1. This “pan-epitope” antibody is useful in therapeutic and prophylactic compositions and treatments of HIV-1 infection, regardless of strain. This pan-epitope antibody is useful in assays for the detection of levels of HIV-1 based on a measurement of the amount of Tat protein in a biological sample.

Abstract: A self-adjuvanting immunogenic composition comprising an immunogen comprising a lipopeptide cap (R2), a universal T helper sequence (R1) and an immunodominant A? B cell epitope. The immunogen also comprises one or more linker sequences and/or polar charged amino acid sequences. The B cell epitope of each immunogen has an amino acid sequence located within the first 17 amino acids of SEQ ID NO: 1. The lipopeptide is a dipalmitoyl-S-glyceryl-cysteine or a tripalmitoyl-S-glyceryl cysteine or N-acetyl (dipalmitoyl-S-glyceryl cysteine), each with an optional neutral amino acid linker. Optional polar sequences of at least four charged polar amino acids enhance solubility of the immunogen and are located at the carboxy terminal end of R2, optionally flanked by neutral linker amino acids, or elsewhere in the immunogen.

Abstract: A self-adjuvanting immunogenic composition comprising multiple immunogens, each immunogen comprising a lipopeptide cap, a universal T helper sequence and an immunodominant HIV-1 Tat B cell epitope. The immunogen also comprises one or more linker sequences and/or polar charged amino acid sequences. The HIV-1 Tat B cell epitope of each immunogen has an amino acid sequence of V-D-P-Xaa7-L-Xaa9-P-W-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-amide SEQ ID NO: 1, in which the amino acid positions at Xaa7, Xaa9 and Xaa12 are selected from specific amino acid residues choices and in which the amino acid positions at Xaa13-Xaa16 may be absent or specific amino acid residue choices. The lipopeptide is a dipalmitoyl-S-glyceryl-cysteine or a tripalmitoyl-S-glyceryl cysteine or N-acetyl (dipalmitoyl-S-glyceryl cysteine), each with an optional neutral amino acid linker.

Abstract: A method for detecting or measuring HIV-1 Transactivating (Tat) protein in a biological sample comprising contacting the biological sample with an amount of a basic protein effective to reduce interference with binding between anti-HIV-1 Tat Epitope 2 ligand and Tat that is caused by acidic components within the sample or reagents. A more accurate detection and measurement of the amount of HIV-1 Tat in the sample is obtained by binding between the anti-Epitope 2 antibody and the Tat in the sample when the interference is neutralized. A diagnostic kit for use in practicing the method contains these components.

Abstract: A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-terminal Pro). Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Abstract: A single isolated antibody or antibody fragment thereof binds to multiple variant sequences within an epitope of HIV-1 Tat protein displayed in multiple strains and subtypes of HIV-1. This “pan-epitope” antibody is useful in therapeutic and prophylactic compositions and treatments of HIV-1 infection, regardless of strain. This pan-epitope antibody is useful in assays for the detection of levels of HIV-1 based on a measurement of the amount of Tat protein in a biological sample.

Abstract: A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-terminal Pro). Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Abstract: A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y7-Leu-X9-Pro-Trp-Z12-R2 (SEQ ID NO: 8). In this composition, at least one of the two variants contains Arg at Y7 and Lys at Z12, and in at least a second of the two variants Y7 is Asn and Z12 is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Abstract: A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-terminal Pro). Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Abstract: A composition which elicits antibodies to multiple known variants of Tat protein of HIV-1 of both the B and non-B clades contains the peptide R1-Asp-Pro-Asn-Leu-Asp-Pro-Trp-Asn-R2 SEQ ID NO: 23, and preferably an additional at least two variants of a peptide or polypeptide of the formula: R1-Asp-Pro-Y7-Leu-X9-Pro-Trp-Z12-R2 (SEQ ID NO: 8). In this composition, at least one of the two variants contains Arg at Y7 and Lys at Z12, and in at least a second of the two variants Y7 is Asn and Z12 is Asn. Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, associated in multiple antigenic peptides or as part of recombinant proteins. Diagnostic compositions and uses are described for assessing the immune status of vaccinated patients.

Abstract: A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-terminal Pro). Vaccinal and pharmaceutical compositions can contain the antibodies induced by the peptide compositions for use in passive therapy.

Abstract: A composition which elicits antibodies to greater than 95%, and even greater than 99%, of the known variants of HIV-1 Tat protein contains at least one peptide or polypeptide of the formula of Epitope I (based on amino acids 2-10 of HIV-1 Tat consensus sequence) and optionally one or more of a peptide or polypeptide of Epitope II (based on amino acids 41 to 51 of that sequence), of Epitope III (based on amino acids 52-62 of that sequence), or of Epitope IV (based on amino acids 62 through 72 of that sequence with a C-termninal Pro). Vaccinal and pharmaceutical compositions can contain one or more such peptides associated with carrier proteins, in multiple antigenic peptides or as part of recombinant proteins. Various combinations of the Epitope I through IV peptides can provide other compositions useful in eliciting anti-Tat antibodies which cross-react with multiple strains and variants of HIV-1 Tat protein.