| 摘要 |
<p>#CMT# #/CMT# Peptide (I) that contains an epitope consisting of sequences (SEQ ID NOs: 1-3) and is not longer than 24 amino acids is new. #CMT# : #/CMT# Peptide (I) that contains an epitope consisting of sequences (SEQ ID NOs: 1-3) and is not longer than 24 amino acids is new. Tyr-Lys-Thr-Leu-Arg-Ala-Glu-Gln-Ala-Ser-Gln-Glu-Val-Lys-Asn-Trp-Met-Thr-Glu-Thr (SEQ ID NO: 1) Leu-Leu-Val-Gln-Asn-Ala-Asn-Pro-Asp-Cys-Lys-Thr-Ile-Leu-Lys-Ala-Leu-Gly-Pro-Ala (SEQ ID NO: 2) SEQ ID NOs: 1-3Lys-Thr-Ile-Leu-Lys-Ala-Leu-Gly-Pro-Ala-Ala-Thr-Leu-Glu-Glu-Met-Met-Thr-Ala-Cys (SEQ ID NO: 3). Independent claims are also included for the following: (1) multiepitope peptide (Ia) that includes at least one of (SEQ ID NOs: 1-3); (2) (I) where associated with a biotinylated complex consisting of the a and b-chains (DRa, b) of a HLA (= human leucocyte antigen), a spacer arm and streptavidin to form a class II tetramer; (3) nucleic acid (NA) that encodes at least one (I) or (Ia); (4) expression vector that contains NA; (5) antibody (Ab) that binds specifically to (SEQ ID NOs: 1-3); (6) isolated antigen-presenting cell (APC) associated with at least one (I), NA and/or vector of (4); (7) isolated clone of T helper cells comprising a receptor specific for a complex of HLA-DR1 and (I); (8) diagnostic methods for determining the immune status of a subject susceptible to HIV infection; and (9) diagnostic kit containing at least one (I) or the tetramer of (2). #CMT#ACTIVITY : #/CMT# Anti-HIV. No details of tests for anti-HIV activity are given. #CMT#MECHANISM OF ACTION : #/CMT# Vaccine; (I) bind to HLA-DR1 to induce an immune response, dependent on CD4+ T cells, against HIV antigens. #CMT#USE : #/CMT# (I), also nucleic acid (NA) that encodes them, and/or vectors that contain NA, are used for treatment and/or prevention of HIV infection; also (I), or complexes containing it, are used for diagnosis and quantification of the immune status of a subject susceptible to HIV (claimed), including monitoring the response to treatment. Antibodies that bind specifically to (I) are useful for diagnosis and/or treatment of HIV and T helper cells associated with (I) are used for prevention and/or treatment. #CMT#BIOTECHNOLOGY : #/CMT# Preferred Peptides: (SEQ ID NOs: 1-3) are derived from the p24 antigen of HIV Gag protein. They are produced by standard chemical synthesis or recombinant DNA methods. Isolation: The Gag protein sequence was scanned, using the algorithm TEPITOPE, for motifs specific for HLA-DR1 to identify sequences (SEQ ID NOs: 1-3), representing, respectively, amino acids 301-320; 321-340 and 331-350 of Gag. They are present at frequencies of 56.7-64.8% in group B HIV-1 strains. Their immunogenicity was confirmed in transgenic HLA-DR1 mice (H2 Class II inactivated) by injection with p24 and restimulation of spleen cells in vitro with the new peptides, to indicate a proliferative response. #CMT#PHARMACEUTICALS : #/CMT# Preferred Composition: (I), NA and/or the vector is associated with a vehicle, i.e. a liposome; exosome or antigen-presenting cell, particularly a dendritic cell. Preferred Process: For diagnosis (1) T helper cells from the test subject are treated in vitro with at least one (I) and the biological response (proliferation; secretion of molecules; and/or appearance/disappearance of cell-associated molecules) is evaluated or (2) lymphocytes isolated from the subject are activated by contact with a complex comprising HLA-DR1 and (I) (specifically the tetramer of (2)) and then quantified. Particularly the biological response is secretion of interferon-gamma . #CMT#ADMINISTRATION : #/CMT# (I)-containing compositions are administered topically, orally, locally or parenterally (intravenous, subcutaneous, intradermal or intramuscular) and the usual dose for a 70 kg subject is 0.1-30, preferably about 15, mg/day. #CMT#EXAMPLE : #/CMT# Peripheral blood mononuclear cells from a HLA-DR1, HIV-negative subject were primed in vitro with autologous dendritic cells, loaded with the HIV antigen p24. The resulting CD4+ T cells were isolated; cultured for 2 weeks in presence of antigen-presenting cells (i.e. irradiated B-EBV autologous cells, loaded with p24), then tested for a proliferative response induced by the 331-350 peptide of HIV Gag. After 3 days, incorporation of tritiated thymidine indicated an index of stimulation of 3.5 (any value over 2 is considered significant).</p> |
