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AssigneePierre Fabre Medicament
InventorsNathalie Corvaia, Thien Nyugen Ngoc, Alain Beck, Helene Plotnicky
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The invention concerns novel immunogenic peptides derived from the RSV G protein of the sub-group A or B comprising at least: a first peptide derived from the BRSV G protein of sub-group A or B including at least in position 173, 176, 182 and 186 a cysteine and whereof the C-terminal end includes at most the amino acid in position 192; and a second peptide derived from the RSV protein of sub-group A or B, said second peptide being located downstream of said first protein, so that the immunogenic peptide produced has a disulphide bond linking residues 173 and 186 and a second disulphide bond linking residues 176 and 182.
1\ An immunogenic peptide derived from the G protein of RSV subgroup A or B comprising at least:
2\ An immunogenic peptide derived from the G protein of RSV subgroup A or B of sequence exhibiting at least 80% homology, after optimal alignment, with the peptide sequence of the immunogenic peptide as claimed in claim 1.
3\ The immunogenic peptide as claimed in claim 1 or 2, characterized in that the C-terminal end of said first peptide comprises at most the amino acid at position 190.
4\ The immunogenic peptide as claimed in claim 1 or 2, characterized in that said first peptide exhibits a sequence chosen from the sequence 130-190, 130-192, 140-190, 140-192, 145-190, 145-192, 148-190, 148-192, 130-188, 140-188, 145-188 or 148-188, and preferably the sequence 140-190.
5\ The immunogenic peptide as claimed in one of claims 1 to 4, characterized in that said second peptide consists of at least one chain of 6 amino acids.
6\ The immunogenic peptide as claimed in one of claims 1 to 5, characterized in that said second peptide contains at least one B epitope of RSV A or B.
7/ The immunogenic peptide as claimed in one of claims 1 to 6, characterized in that said second peptide is chosen from the fragments of the RSV G protein comprising at least the fragment 144-158 of the RSV G protein, the C-terminal end of said second peptide comprising at most the amino acid at position 172.
8\ The immunogenic peptide as claimed in one of claims 1 to 7, characterized in that said second peptide exhibits a sequence chosen from the sequence 144-158 and 144-159 of the RSV G protein.
9\ The immunogenic peptide as claimed in one of claims 1 to 6, characterized in that said second peptide is chosen from the peptides of sequence 221-237, 274-287, 262-268 and 483-488 of the RSV F protein.
10\ The immunogenic peptide as claimed in one of claims 1 to 9, characterized in that said immunogenic peptide derived from the G protein of RSV subgroup A or B exhibits negative immediate hypersensitivity.
11\ The immunogenic peptide as claimed in one of claims 1 to 10, characterized in that said immunogenic peptide derived from the G protein of RSV subgroup A or B exhibits the sequence SEQ ID No.1, SEQ ID No.2 or SEQ ID No.3.
12\ A nucleic acid sequence encoding an immunogenic peptide as claimed in one of claims 1 to 11.
13\ A pharmaceutical composition, characterized in that it contains, in a pharmaceutically acceptable medium, at least one immunogenic peptide as claimed in one of claims 1 to 11 and/or a nucleic acid sequence as claimed in claim 12.
14\ The composition as claimed in claim 13, characterized in that it also contains at least one carrier protein and/or an adjuvant.
15\ The composition as claimed in claim 14, characterized in that the carrier protein consists of derivatives of the DT protein in which at least one cysteine residue has been deleted.
16\ The composition as claimed in claim 15, characterized in that the carrier protein consists of a protein of sequences SEQ ID No.4, SEQ ID No.5 and SEQ ID No.6.
17\ The composition as claimed in claim 14, characterized in that the adjuvant is chosen from the adjuvant group comprising MPL-A, MF59, Quil-A, ISCOM, dimethyldioctadecylammonium bromide (DDAB) or dimethyldioctadecyl-ammonium chloride (DDAC), alumina, adjuphos, CpGs, Leif, CT, LT and detoxified versions of CT or LT.
18\ The composition as claimed in one of claims 13 to 17, characterized in that said immunogenic peptide is associated, by mixing or by coupling, with the carrier protein and/or with the adjuvant.
19\ The composition as claimed in one of claims 13 to 18, characterized in that said pharmaceutical composition also contains a second antigen, immunogen or hapten of RSV and/or an antigen, immunogen or hapten derived from a microorganism responsible for pathologies of the airways, chosen from parainfluenza viruses (PIV 1, 2, 3 and 4), influenza virus (A and B), hantaviruses, streptococci, pneumococci, hemophilus influenza type b, rhinoviruses, coronaviruses and meningococci.
20\ The composition as claimed in one of claims 13 to 19, characterized in that said pharmaceutically acceptable medium consists of water, of a saline aqueous solution or of an aqueous solution based on dextrose and/or on glycerol.
21\ The composition as claimed in one of claims 13 to 20, characterized in that said pharmaceutical composition is vehiculed in a form which makes it possible to improve its stability and/or its immunogenicity.
22\ A polyclonal or monoclonal antibody directed against an immunogenic peptide as claimed in one of claims 1 to 11.
23\ The antibody as claimed in claim 22, characterized in that it is humanized.
24\ A diagnostic kit, characterized in that it comprises an immunogenic peptide as claimed in one of claims 1 to 11, a nucleic acid sequence as claimed in claim 9 or an antibody as claimed in claim 22 or 23.
25\ The use of an immunogenic peptide as claimed in one of claims 1 to 11, of a nucleic acid sequence as claimed in claim 12 or of an antibody as claimed in claim 22 or 23, for preparing a pharmaceutical composition intended for the prophylactic or therapeutic treatment of conditions caused by RSV, subgroup A or B, which exhibits an immunogenic response, RSV A and B cross protection and negative immediate hypersensitivity and which does not induce immunopathologies.
26\ The use of an immunogenic peptide as claimed in one of claims 1 to 11, of a nucleic acid sequence as claimed in claim 12 or of an antibody as claimed in claim 22 or 23, for preparing a pharmaceutical composition intended to generate or increase an immune response against RSV.
27\ A conjugate of sequences SEQ ID No.7, SEQ ID No.8 and SEQ ID No.9.