Identification and Attenuation of the Immunosuppressive Domains in Fusion Proteins of Enveloped RNA Viruses

1 .- 66 . (canceled)

67 . A peptide providing immunosuppressive properties, said peptide comprising an amino acid sequence selected from the sequences shown in Table 1 or selected from SEQ ID NOS:1-200.

68 . The peptide according to claim 1 comprising the amino acid sequence of an immunosuppressive domain.

69 . A peptide having the amino acid sequence of an immunosuppressive domain, said peptide identified by a method for identifying an immunosuppressive domain in a fusion protein of an enveloped RNA virus having a lipid membrane, said method comprising:

a) identifying at least one well-conserved domain among the group consisting of the membrane-associated domains of the fusion protein and the surface-associated domains of the fusion protein;

b) providing at least one peptide with the sequence of said identified at least one well-conserved domain;

c) optionally dimerizing or multimerizing said at least one peptide; and

d) testing said at least one peptide or said at least one optionally dimerized or multimerized peptide for immunosuppressive activity.

70 . The peptide according to claim 69 , wherein said at least one peptide is dimerized or multimerized.

71 . The peptide according to claim 3 , wherein the identification of said at least one well-conserved domain is performed using the group consisting of the surface-associated domains of the fusion protein in one or more different conformations of the fusion protein undergoing fusion.

72 . A mutated peptide providing reduced immunosuppressive properties, said mutated peptide comprising a mutated sequence selected from SEQ ID NOS:201-203 or a variant of an amino acid sequence selected from the sequences shown in Table 1 or selected from SEQ ID NOS:1-200, wherein said mutated sequence comprises from 1 to 4 amino acid substitutions, or at least one amino acid insertion, or at least one amino acid deletion.

73 . A mutated peptide providing reduced immunosuppressive properties, said mutated peptide being obtainable as a selected mutated peptide by a method for decreasing or completely abrogating the immunosuppressive properties of an immunosuppressive domain of a fusion protein of an enveloped RNA virus having a lipid membrane, said method comprising the steps of:

a) mutating an immunosuppressive domain of said fusion protein to provide at least one mutated peptide;

b) optionally dimerizing or multimerizing said at least one mutated peptide;

c) selecting one of said at least one mutated peptide or said at least one optionally dimerized or multimerized mutated peptide showing reduced immunosuppressive properties;

d) preparing a mutant of said at least one fusion protein or said at least one optionally dimerized or multimerized mutated peptide containing said selected mutated peptide having reduced immunosuppressive properties; and

e) confirming expression of said at least one mutated fusion protein or said at least one optionally dimerized or multimerized mutated peptide on a cell surface or a viral envelope surface.

74 . The mutated peptide according to claim 73 , wherein a plurality of mutated peptides are provided in step (a), optionally utilized in step (b), and utilized in steps (c)-(e).

75 . The mutated peptide according to claim 73 , wherein said at least one mutated peptide or said at least one optionally dimerized or multimerized mutated peptide has immunosuppressive properties which are reduced by at least 25% compared to a dimerized wildtype version of the same peptide(s).

76 . The mutated peptide according to claim 73 , wherein said mutated immunosuppressive domain is selected from SEQ ID NOS:201-203 or is mutated to provide a knock-out mutant of a sequence selected from the sequences shown in Table 1 or selected from SEQ ID NOS:1-200.

77 . An enveloped RNA virus that is not a retrovirus, lentivirus, or filovirus, wherein an immunosuppressive domain of a fusion protein of the virus has been modified or mutated to decrease or completely abrogate immunosuppression by an immunosuppressive domain of the fusion protein.

78 . A virus selected from the viruses shown in Table 1 comprising an immunosuppressive domain that has been modified or mutated to decrease or completely abrogate immunosuppression by an immunosuppressive domain of a fusion protein of the virus.

79 . A vaccine composition comprising a virus according to claim 78 .

80 . A vaccine composition comprising an envelope protein from a virus according to claim 78 .

81 . A method of treating or ameliorating a symptom caused by a virus infection of an individual, or prophylactically treating an individual, the method comprising administering an effective amount of the vaccine composition according to claim 79 .

82 . A method of reducing or abolishing an immune response in an individual, the method comprising administering to said individual an effective amount of the peptide according to claim 67 .

83 . The method according to claim 82 , wherein the immune response comprises cytokine secretion or proliferation of T-cells.