Anti-varicella-zoster virus antibody
The present invention relates to neutralizing monoclonal antibodies or antigen-binding fragments thereof that are specific for and bind with high affinity to Varicella-Zoster Virus, and a preparation method for producing such antibodies. The antibodies of the present invention have high efficiency in neutralizing Varicella-Zoster Virus infection. The present invention also relates to the epitope to which the antibodies bind and the use of the antibodies in the diagnosis, prevention and treatment of infected individuals.
1 . An isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof, comprising three complementarity determining region CDRs of the heavy chain variable region and three complementarity determining region CDRs of the light chain variable region, wherein
(i) CDR1 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 7, CDR2 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 8, CDR3 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 9, and CDR1 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 10, CDR2 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 11, and CDR3 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 12;
(ii) CDR1 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 1, CDR2 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 2, CDR3 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 3, and CDR1 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 4, CDR2 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 5, and CDR3 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 6; or
(iii) CDR1 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 13, CDR2 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 14, CDR3 of the heavy chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 15, and CDR1 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 16, CDR2 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 17, and CDR3 of the light chain variable region comprises the amino acid sequence as shown in SEQ ID NO: 18.
2 . The isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 , comprising a heavy chain variable region and a light chain variable region, wherein
(i) the heavy chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 21 or an amino acid sequence as shown in SEQ ID NO: 21, and the light chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 22 or an amino acid sequence as shown in SEQ ID NO: 22; or
(ii) the heavy chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 19 or an amino acid sequence as shown in SEQ ID NO: 19, and the light chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 20 or an amino acid sequence as shown in SEQ ID NO: 20; or
(iii) the heavy chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 23 or an amino acid sequence as shown in SEQ ID NO: 23, and the light chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 24 or an amino acid sequence as shown in SEQ ID NO: 24; or
(iv) the heavy chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 25 or an amino acid sequence as shown in SEQ ID NO: 25, and the light chain variable region comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 26 or an amino acid sequence as shown in SEQ ID NO: 26.
3 . The isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is a human monoclonal antibody.
4 . The isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab′-SH, Fv, scFv and (Fab′) 2 fragment.
5 . The isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 , comprising a heavy chain and a light chain constant region sequences, wherein the heavy chain and light chain constant region sequences are human IgG1 heavy chain and light chain constant region sequences.
6 . An isolated nucleic acid encoding the isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 .
7 . A vector comprising the nucleic acid of claim 6 .
8 . A host cell comprising the vector of claim 7 , wherein the host cell is a prokaryotic cell or a eukaryotic cell.
9 . A method of preparing an anti-VZV monoclonal antibody or antigen-binding fragment thereof, comprising culturing the host cell of claim 8 under a condition suitable for expressing the anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 .
10 . A pharmaceutical composition comprising the anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 and a pharmaceutical carrier.
11 . A method of treating a human individual infected with Varicella-Zoster Virus or having Varicella-Zoster Viral disease, comprising administering to the individual in need of the treatment an effective amount of the pharmaceutical composition of claim 10 .
12 . A method of enhancing the resistance of a human individual to Varicella-Zoster Virus infection, comprising administering to the individual in need thereof an effective amount of the pharmaceutical composition of claim 10 .
13 . The method of claim 11 , wherein the individual is immunocompromised.
14 . The method of claim 11 , wherein the individual is a newborn baby, premature baby, woman in childbirth, and immune insufficiency subject receiving immunosuppressive agents, cytotoxic drugs or radiotherapy due to an organ transplant operation, hematological malignancy, malignant tumor, or nephrotic syndrome.
15 . A method of neutralizing Varicella-Zoster Virus in a subject or sample, comprising adding an appropriate amount of the anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 1 to the subject or sample.
16 . The method of claim 12 , wherein the individual is immunocompromised.
17 . The method of claim 12 , wherein the individual is a newborn baby, premature baby, woman in childbirth, and immune insufficiency subject receiving immunosuppressive agents, cytotoxic drugs or radiotherapy due to an organ transplant operation, hematological malignancy, malignant tumor, or nephrotic syndrome.
18 . The host cell according to claim 8 , wherein the host cell is selected from yeast cells, or mammalian cells.
19 . The isolated anti-VZV monoclonal antibody or antigen-binding fragment thereof according to claim 2 , comprising a heavy chain and a light chain constant region sequences, wherein the heavy chain and light chain constant region sequences are human IgG1 heavy chain and light chain constant region sequences.