Method for inducing an immune response against avian, swine, spanish, H1N1, H5N9 influenza viruses and formulations thereof

A peptide heteroconjugate, comprising a peptide construct consisting of the formula P1-x-P2 or P2-x-P1, wherein

• P1 represents a specific antigenic peptide originating from an influenza virus and competent for recognition by a class or subclass of immune cells or binding to an antibody;
• P2 represents an immunomodulatory peptide which is a portion of an immunoprotein capable of promoting binding to a class or subclass of immune cells and directing a subsequent immune response to the peptide P1;
• and
• x represents a covalent bond or a divalent linking group,
• wherein P2 is a peptide sequence selected from SEQ ID Nos. 3 and 6 or a variant thereof;
• wherein the variant is selected from the group consisting of:
• i) modification to either or both of an N- or C-terminal of the sequence by any one or more of amidation or acylation;
• ii) deletion of 1, 2, 3, 4, or 5 amino acids from the sequence;
• iii) addition of 1, 2, 3, 4, or 5 amino acids to the sequence;
• and
• iv) substitution of 1, 2, 3, 4 or 5 amino acids in the sequence,
• wherein the peptide construct comprises a sequence of amino acids selected from the group of SEQ ID Nos. 7-10, wherein SEQ ID Nos. 7-10 is an antigen from an influenza virus.

A vaccine for immunization of a mammal against Type A influenza virus comprising an immunologically effective amount of a peptide heteroconjugate(s) consisting of a sequence selected from the group consisting of SEQ ID Nos. 1-2 and 15-32 or a variant thereof, optionally in combination with an adjuvant;

• wherein the variant is selected from the group consisting of:
• i) modification to either or both of an N- or C-terminal of the sequence by any one or more of amidation or acylation;
• ii) deletion of 1, 2, 3, 4, or 5 amino acids from the sequence;
• iii) addition of 1, 2, 3, 4, or 5 amino acids to the sequence;
• and
• iv) substitution of 1, 2, 3, 4 or 5 amino acids in the sequence,
• wherein the peptide construct comprises a sequence of amino acids selected from the group of SEQ ID Nos. 7-10, wherein SEQ ID Nos. 7-10 is an antigen from an influenza virus.

A therapeutic method, comprising administering an immunologically effective amount of a peptide heteroconjugate consisting of a sequence selected from the group consisting of SEQ ID Nos. 1-2 and 15-32 or variants thereof, optionally with an adjuvant;

• wherein the variant is selected from the group consisting of:
• i) modification to either or both of an N- or C-terminal of the sequence by any one or more of amidation or acylation;
• ii) deletion of 1, 2, 3, 4, or 5 amino acids from the sequence;
• iii) addition of 1, 2, 3, 4, or 5 amino acids to the sequence;
• and
• iv) substitution of 1, 2, 3, 4 or 5 amino acids in the sequence,
• wherein the peptide construct comprises a sequence of amino acids selected from the group of SEQ ID Nos. 7-10, wherein SEQ ID Nos. 7-10 is an antigen from an influenza virus.

A method for modulating a response to Type A influenza virus in a subject in need thereof, comprising:

• combining precursors of dendritic cells taken from the blood, bone marrow, spleen, or other suitable source with a peptide heteroconjugate(s) consisting of a sequence selected from the group consisting of SEQ ID Nos. 1-2 and 15-32 or a variant thereof ex vivo to form a mixture, and incubating from one hour to several days to allow maturation to form more mature dendritic cells, and
• administering the mixture to the same subject from which the precursors of dendritic cells were taken or to a genetically compatible subject;
• wherein the variant is selected from the group consisting of:
• i) modification to either or both of an N- or C-terminal of the sequence by any one or more of amidation or acylation;
• ii) deletion of 1, 2, 3, 4, or 5 amino acids from the sequence;
• iii) addition of 1, 2, 3, 4, or 5 amino acids to the sequence;
• and
• iv) substitution of 1, 2, 3, 4 or 5 amino acids in the sequence,
• wherein the peptide construct comprises a sequence of amino acids selected from the group of SEQ ID Nos. 7-10, wherein SEQ ID Nos. 7-10 is an antigen from an influenza virus.