Human anti-human influenza virus antibody
Provided is a human antibody having a neutralization activity against a human influenza virus. More specifically, provided is a human antibody which recognizes a highly conserved region in a human influenza A virus subtype H3N2 or a human influenza B virus and has a neutralization activity against the virus. The human antibody is a human anti-human influenza virus antibody, which has a neutralization activity against a human influenza A virus subtype H3N2 and binds to a hemagglutinin HA1 region of the human influenza A virus subtype H3N2, or which has a neutralization activity against a human influenza B virus, and includes, as a base sequence of a DNA encoding a variable region of the antibody, a sequence set forth in any one of SEQ ID NOS: 5 to 12.
1. An isolated human anti-human influenza virus antibody, which has a neutralization activity against a human influenza A virus subtype H3N2 and binds to a hemagglutinin HA1 region of the human influenza A virus subtype H3N2, wherein an epitope recognized by the isolated antibody comprises an amino acid sequence including an amino acid sequence set forth in SEQ ID NO: 1 or 2.
2. An isolated human anti-human influenza virus antibody according to claim 1 , wherein the isolated human anti-human influenza virus antibody is free of a neutralization activity against human influenza A virus subtypes H1 and H2.
3. An isolated human anti-human influenza virus antibody according to claim 1 , wherein the isolated human anti-human influenza virus antibody, which has a neutralization activity against a human influenza A virus subtype H3N2, has a neutralization activity against at least an A/Hiroshima/52/05 strain.
4. An isolated human anti-human influenza virus antibody, comprising a variable region comprising:
a heavy chain comprising the amino acid sequence of SEQ ID NO: 27 and a light chain comprising the amino acid sequence of SEQ ID NO: 28; or
a heavy chain comprising the amino acid sequence of SEQ ID NO: 29 and a light chain comprising the amino acid sequence of SEQ ID NO: 30.
5. An isolated human anti-human influenza virus antibody according to claim 1 , wherein the isolated antibody comprises an isolated intact antibody.
6. A DNA, which encodes a variable region of an isolated human anti-human influenza virus antibody, which has a neutralization activity against a human influenza A virus subtype H3N2 and binds to a hemagglutinin HA1 region of the human influenza A virus subtype H3N2, the DNA comprising a polynucleotide which is selected from a base sequence set forth in any one of SEQ ID NOS: 5 to 8 or which includes any of base sequence having substitutions of one or more nucleotides in the base sequence, and which encodes SEQ ID NOS: 27-30, respectively,
1)
(SEQ ID NO: 5)
GAGGAGAACCTGTTGCAGTCTGGGGGAGGCTTGGTCCAGCCGGGGGGGTC
CCTGAGACTCTCCTGTGCAGGCTCTGGATTCACGTTTAGTACTTACGCCA
TGACCTGGGTCCGCCAGGCTCCAGGACAGGGGCTGGAGTGGGTCTCCTCT
ATTAGCGGTAGTGGTGAAATTTCCTATTACGCAGACTCCGTGAAGGGCCT
GTTCACCATCTCCAGGGACAATTCCAAGGACACAGTGTTTCTGCAAATGA
CCAGCCTGAGAGCCGAAGACACGGCCGTATATTACTGTGCGAAATCCGAC
GTTTGGGAGGGTTATCGACCCTCAAAAGATGCTCTTCATATGTGGGGCCA
AGGGACAATGGTCACCGTCTCTTCA;
2)
(SEQ ID NO: 6)
GACGTCCAGATGACTCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGA
CAGAGTCACCATCACTTGTCGGGCAAGTCAGAGCGTGAGCAATTATGTGA
ATTGGTATCAACAGAAGCCAGGGAGAGCCCCTAGGCTCCTCATCTCTAGT
GCGTCCAATTTGTGGGCTGGGGTCCCGCCAAGGTTCAGTGGCCGTGGAGA
AGAGACAGACTTCACTCTCACCATCACCAGTCTGCAACCTGAAGATTCTG
CAGTTTACTACTGTCAACAGAGTTACAGTGACCTTCTCAGTTTCGGCGGA
GGGACCAAGGTGGAGATCAAA;
3)
(SEQ ID NO: 7)
CAGGTGCAGCTGGTGCAATCTGGGTCTGAGTTGAAGAAGCCTGGGGCCTC
AGTGAAGGTTTCCTGCAAGGCTTCTGGATACACCTTCACCTCTTATTCTA
TATATTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGG
ATCAACACCAACACTGGGAACCCAAGCTATGCCCAGGGCTTCACAGGACG
GTTTGTCTTCTCCTTCGACACCTCTGTCAGCACGGCATATCTGGAGATCA
GCAGCCTAAAGGCTGAGGACACTGCCGTGTATTACTGTGCGAGAGAGGGA
GATTACGATATTTTGACTGGTTATTATTATTACTTTGACTACTGGGGCCA
GGGAACCCTGGTCACCGTCTCCTCA;
and
4)
(SEQ ID NO: 8)
CAGACTGTGGTGACCCAGGAGCCATCGTTCTCAGTGTCCCCTGGAGGGAC
AGTCACACTCACTTGTGGCTTGAGCTCTGGCTCAGTCTCTCCTAGTTACT
ACGCCAGCTGGTACCAGCAGACCCCAGGCCAGGCTCCACGCACGCTCATC
TACAACACAAACACTCGCTCCTCTGGGGTCCCTGATCGCTTCTCTGGCTC
CTTCCTTGGGAGCGACGCTGCCCTCACCATCACGGGGGCCCAGGCAGATG
ATGAGTCTGATTATTTCTGTGTGCTGTATATGCCTAGTGGCGATTGGGTT
TTCGGCGGAGGGACCAAGCTGACCGTCCTAGGT.
7. A composition, comprising the isolated human anti-human influenza virus antibody according to claim 1 .
8. An isolated human anti-human influenza virus antibody according to claim 1 , wherein the isolated human anti-human influenza virus antibody is free of a neutralization activity against human influenza A virus subtypes H1 and H2, and has a neutralization activity against at least an A/Hiroshima/52/05 strain.
9. An isolated human anti-human influenza virus antibody according to claim 1 , wherein the epitope comprises an amino acid sequence including an amino acid sequence set forth in SEQ ID NO: 1.
10. An isolated human anti-human influenza virus antibody according to claim 1 , wherein the epitope comprises an amino acid sequence including an amino acid sequence set forth in SEQ ID NO: 2.
11. The DNA of claim 6 , wherein the DNA comprising a polynucleotide which is selected from a base sequence set forth in any one of SEQ ID NOS: 5 to 8.