Peptide constructs derived from the GP120 C5 domain and GP41 transmembrane domain
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.
1. A peptide combination,
wherein the peptide combination is
(a) selected from the group consisting of disulphide linked peptides between SEQ ID NO: 28 and any one of SEQ ID NOs: 29, 31, and 33; between SEQ ID NO: 30 and any one of SEQ ID NO: 29, 31, and 33; or between SEQ ID NO: 32 and any one of SEQ ID NO: 29, 31, and 33; or
(b) selected from the group consisting of cysteine-lysine linked peptides between SEQ ID NO: 38 and any one of SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, and SEQ ID NO: 43; or between SEQ ID NO: 41 and any one of SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 42, and SEQ ID NO: 43; and
wherein said peptide combination is capable of inducing an antibody which can bind and stabilise the association of the C5 domain of HIV gp120 with the transmembrane domain of gp41 and/or with the constant C2 domain of gp120, and wherein said peptide combination lacks amino acids N-terminal of C5 in gp120.
2. The peptide combination according to claim 1 where at least one of the peptides of the combination comprises an N- or C-terminal modification.
3. The peptide combination according to claim 1 , which is coupled to a carrier molecule.
4. The peptide combination according to claim 3 , wherein the carrier is a virus like particle.
5. The peptide combination of claim 1 , selected from the group consisting of:
6. An immunogenic composition comprising at least one peptide combination according to claim 1 in combination with a pharmaceutically acceptable diluent or vehicle and optionally an immunological adjuvant.
7. The immunogenic composition according to claim 6 in the form of a vaccine composition.
8. A kit for determining the presence of antibodies which bind an epitope composed of amino acids in the C5 domain of gp120 as well as of amino acids in the transmembrane domain of gp41 and/or the constant C2 domain of gp120, the kit comprising at least one peptide combination according to claim 1 , means for reacting a liquid sample with said peptide combination, and means for determining the presence of a positive or negative binding reaction between antibodies and said peptide combination.
9. The peptide combination according to claim 1 , consisting of cysteine-lysine linked peptides between SEQ ID NO: 38 and any one of SEQ ID NO: 39, SEQ ID NO: 40; SEQ ID NO: 42, and SEQ ID NO: 43.