H5 proteins of h5n1 influenza virus for use as a medicament

A method of treating or preventing infections with H5N1 virus of a different clade comprising administering to a subject an H5 protein of clade 1 H5N1 virus, wherein said H5 protein comprises a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1, wherein said H5N1 virus of a different clade is a H5N1 virus comprising:

• a. a polynucleotide encoding a second H5 protein comprising:
• i. the amino acids 87L, 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, or
• ii. the amino acids 87P, 113N, 126R, 145L, 160Y, 172T, 181H, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 87L, 113N, 126R, 145L, 156G, 160Y, 172T, 181H, and 254V,
• wherein the numbering of the amino acid positions of the second H5 protein of group (i), (ii), and (iii) refers to the amino acid position as exemplarily given in SEQ ID NO:8;
• or
• iv. any one of the amino acid sequences of SEQ ID NOs:
• 62 to 137;
• or
• b. a second H5 protein comprising any peptide that has at least 85%, preferably at least 95%, even more preferably at least 96%, even more preferably at least 97%, even more preferably at least 98%, even more preferably at least 99%, most preferably 100% sequence homology to the polypeptide of i) and that comprises hemagglutinin inhibition in a standard hemagglutinin inhibition assay;
• or
• c. a second H5 protein comprising any part of the polypeptides of a.i) or a.ii) comprising at least 334 contiguous amino acids of any of such peptides of a.i) or a.ii) and wherein any of such peptide comprises hemagglutinin inhibition in a standard hemagglutinin inhibition assay;
• or
• d. a second H5 protein of influenza virus, wherein said second H5 protein comprises a contiguous amino acid sequence which has at least 95% even more preferably at least 96%, even more preferably at least 97%, even more preferably at least 98%, even more preferably at least 99%, most preferably 100% sequence identity with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A method for the prophylaxis or treatment of infections caused by H5N1 virus of a clade other than clade 1 comprising administering to a subject a pharmaceutical composition, preferably of a single-shot vaccine or a one dose vaccine comprising an H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1, wherein said H5N1 virus of a different clade is a H5N1 virus comprising:

• a. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• i. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• ii. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 145L, 172T, and 254V, wherein the numbering of the amino acid positions of the second H5 protein of group (i), (ii), and (iii) refers to the amino acid position as exemplarily given in SEQ ID NO:8;
• or
• iv. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46;
• or
• b. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A method for the treatment or prophylaxis of influenza virus infections caused by H5N1 virus of a clade other than clade 1, comprising administration of a therapeutically effective amount of the H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1 to a subject in need of such a treatment, wherein said H5N1 virus of a clade other than clade 1 is a H5N1 virus comprising:

• a. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• i. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• ii. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 145L, 172T, and 254V,
• wherein the numbering of the amino acid positions of the second H5 protein of group (i), (ii), and (iii) refers to the amino acid position as exemplarily given in SEQ ID NO:8, or
• iv. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46;
• or
• b. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A method for the treatment or prophylaxis of influenza virus infections caused by H5N1 virus of a clade other than clade 1, comprising administration of a therapeutically effective amount of a vaccine comprising an H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1, and a pharmaceutical acceptable carrier and/or excipient to a subject in need of such a treatment, wherein said H5N1 virus of a clade other than clade 1 is a H5N1 virus comprising:

• a. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• i. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• ii. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 145L, 172T, and 254V,
• wherein the numbering of the amino acid positions of the second H5 protein of group (a), (b), and (c) refers to the amino acid position as exemplarily given in SEQ ID NO:8, or
• iv. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46;
• or
• b. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A kit of parts, that comprises:

• a. an H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1;
• and
• b. a package leaflet indicating the use of such H5 protein according to a) for the treatment or prophylaxis of infections caused by H5N1 virus of a clade other than clade 1, wherein said H5N1 virus of a clade other than clade 1 is a H5N1 virus comprising:
• i. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• 1. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• 2. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• 3. the amino acids 145L, 172T, and 254V,
• wherein the numbering of the amino acid positions of the second H5 protein of group (1), (2), and (3) refers to the amino acid position as exemplarily given in SEQ ID NO:8;
• or
• 4. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46;
• or
• ii. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A method of reducing the incidence of or severity of influenza infection, said influenza infection being with a H5N1 virus of a different clade, said method comprising the step of administering a composition comprising the H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1, wherein said H5N1 virus of a different clade is a H5N1 virus of a clade other than clade 1 comprising:

• a. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• i. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• ii. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 145L, 172T, and 254V, wherein the numbering of the amino acid positions of the second H5 protein of group (i), (ii), and (iii) refers to the amino acid position as exemplarily given in SEQ ID NO:8;
• or
• iv. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46, or
• b. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A method for reducing viral shedding in a subject comprising administering to said subject an H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1, wherein said H5 protein is to be administered to a subject infected with or at risk of a viral infection with H5N1 virus of a clade other than clade 1, and wherein said H5N1 virus of a clade other than clade 1 is a H5N1 virus comprising:

• a. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• i. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• ii. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 145L, 172T, and 254V, wherein the numbering of the amino acid positions of the second H5 protein of group (i), (ii), and (iii) refers to the amino acid position as exemplarily given in SEQ ID NO:8;
• or
• iv. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46;
• or
• b. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.

A method for reducing viral shedding in a subject infected with or at risk of a viral infection with H5N1 virus of a clade other than clade 1 comprising administering to said subject a medicament comprising an H5 protein comprising a polypeptide sequence having at least 98% sequence identity with the polypeptide sequence of SEQ ID NO:1, wherein said H5N1 virus of a clade other than clade 1 is a H5N1 virus comprising:

• a. a polynucleotide encoding a second H5 protein of influenza virus, wherein said second H5 protein encodes an amino acid sequence comprising:
• i. the amino acids 113D, 126H, 145(−), 156R, 160F, 167T, and 181N, wherein the modification 145(−) means that amino acid position 145 of H5 is deleted, or
• ii. the amino acids 87P, 145L, 172T, 201E, 206I, 208K, 254T, 341G and 421K, or
• iii. the amino acids 145L, 172T, and 254V,
• wherein the numbering of the amino acid positions of the second H5 protein of group (i), (ii), and (iii) refers to the amino acid position as exemplarily given in SEQ ID NO:8;
• or
• iv. an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137 or 9 to 46;
• or
• b. a second H5 protein of influenza virus, wherein said second H5 protein comprises an amino acid sequence which is at least 95%, preferably at least 96%, more preferably at least 97%, still more preferably at least 98%, yet more preferably at least 99%, or in particular preferred 100% homolog with any one of the sequences as set forth in SEQ ID NOs:
• 62 to 137.