CN-121991211-A - Single domain antibody specifically binding to fever with thrombocytopenia syndrome virus Gn protein

Abstract

The invention discloses a single domain antibody specifically binding to a Gn protein of a fever with thrombocytopenia syndrome virus. Experiments prove that the antibody has strong binding activity to the Gn protein of the fever with thrombocytopenia syndrome virus, obvious neutralization effect of pseudoviruses and live viruses, and high purity after humanization. The invention can be used for preparing medicines for treating or preventing diseases caused by fever with thrombocytopenia syndrome virus infection, and provides a new means for preventing and controlling related diseases.

Inventors

• GAO CHAO
• SHEN WEIQIANG

Assignees

• 南京赛乐思生物制药有限公司

Dates

Publication Date

20260508

Application Date

20260227

Claims (10)

1. 1. A single domain antibody or antigen binding fragment thereof that specifically binds to the Gn protein of the febrile and thrombocytopenia syndrome virus, characterized in that the single domain antibody or antigen binding fragment thereof comprises heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, the amino acid sequences of the heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3 being shown in SEQ ID No.1, SEQ ID No. 2 and SEQ ID No. 3, respectively.
2. 2. The single domain antibody or antigen binding fragment thereof that specifically binds to the Gn protein of the febrile concomitant thrombocytopenia syndrome virus according to claim 1, wherein the single domain antibody or antigen binding fragment thereof comprises a heavy chain variable region having an amino acid sequence as set forth in any one of SEQ ID NOs 4 to 8.
3. 3. An immunoglobulin comprising the single domain antibody or antigen binding fragment thereof of claim 1 or 2 that specifically binds to the Gn protein of the febrile concomitant thrombocytopenia syndrome virus and an immunoglobulin Fc region.
4. 4. The immunoglobulin of claim 3 wherein the immunoglobulin Fc region comprises a CH2 domain and a CH3 domain.
5. 5. An immunoglobulin according to claim 3, wherein the immunoglobulin Fc region is selected from IgG or IgA.
6. 6. Immunoglobulin according to claim 5, characterized in that the immunoglobulin Fc region is selected from human IgG1, igG2, igG3 and/or IgG4 or an Fc region amino acid sequence having one or more amino acid mutations (preferably substitutions, insertions or deletions) with human IgG1, igG2, igG3, igG 4.
7. 7. An immunoglobulin according to claim 3, wherein the immunoglobulin comprises a chimeric antibody or antigen-binding fragment thereof, and/or a humanized antibody or antigen-binding fragment thereof.
8. 8. An immunoglobulin according to claim 3, comprising an amino acid sequence as set forth in any one of SEQ ID NOs 9 to 13.
9. 9. A nucleic acid molecule encoding the single domain antibody or antigen binding fragment thereof of claim 1 or 2 or the immunoglobulin of any one of claims 3-8.
10. 10. Use of a single domain antibody or antigen binding fragment thereof according to claim 1 or 2, an immunoglobulin according to any one of claims 3-8 or a nucleic acid molecule according to claim 9 for the manufacture of a medicament for the treatment or prevention of a disease caused by infection with a febrile thrombocytopenia syndrome virus.

Description

Single domain antibody specifically binding to fever with thrombocytopenia syndrome virus Gn protein Technical Field The invention belongs to the field of biological medicine, and in particular relates to a single domain antibody or an antigen binding fragment thereof which specifically binds to a Gn protein of a fever with thrombocytopenia syndrome virus. Background Fever with thrombocytopenia syndrome virus (SEVERE FEVER WITH thrombocytopenia syndrome virus, SFTSV) is a new tick-borne virus of the genus Brucella, the order Brucoviridae, old-type opera school, the main transmission medium of which is long-angle blood ticks, and the risk of people transmission through blood contact exists, and the virus is widely popular in multiple provinces in the middle east of China and in eastern Asia countries such as Japan, korea, vietnam and the like, and constitutes a serious threat to public health safety. The clinical manifestation of the virus after infection takes high fever, hypodynamia and muscle soreness as initial symptoms, then the symptoms progress to thrombocytopenia and leucopenia rapidly, severe patients can suffer from multi-organ failure, the death rate is as high as 12% -30%, and the disease is one of pathogens which need to be paid priority to by the world health organization. There is currently no specific therapy or effective antibody treatment for SFTSV infection, only a partial treatment regimen. For example, physical or pharmaceutical antipyretic is performed for fever, plasma is infused for thrombocytopenia, platelets. SFTSV has a high mortality rate and serious clinical hazard. SFTSV envelope proteins include Gn and Gc, with Gn playing a necessary role for the receptor on the virus binding target cell. In the antibody medicine of the target spot, the SNB02 nano antibody can target Gn protein of virus and is in preclinical stage. Preclinical data show that SNB02 cannot achieve complete viral clearance, and can only reduce viral load to some extent, improving symptoms after SFTSV infection. Therefore, an antibody aiming at the Gn protein of the virus is developed, and the virus replication can be rapidly inhibited, so that the clinical symptoms are relieved, the survival rate of patients is improved, and the urgent clinical demands can be solved. Disclosure of Invention In view of the above, the present invention has developed a single domain antibody capable of specifically binding to the Gn protein of the fever with thrombocytopenia syndrome virus to obtain a more excellent clinical therapeutic effect. The specific antibody of the invention provides a new effective means for preventing and treating diseases caused by SFTSV infection. Specifically, the invention provides a single domain antibody or an antigen binding fragment thereof which specifically binds to a Gn protein of a fever with thrombocytopenia syndrome virus, wherein the single domain antibody or the antigen binding fragment thereof comprises heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, and the amino acid sequences of the heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3 are shown as SEQ ID NO. 1, SEQ ID NO. 2 and SEQ ID NO. 3 respectively. In certain embodiments, the single domain antibody or antigen binding fragment thereof comprises a heavy chain variable region having an amino acid sequence as set forth in any one of SEQ ID NOs 4-8. The invention also provides an immunoglobulin comprising the single domain antibody or antigen binding fragment thereof specifically binding to the Gn protein of the febrile thrombocytopenia syndrome virus and an immunoglobulin Fc region. In certain embodiments, the immunoglobulin Fc region comprises a CH2 domain and a CH3 domain. In certain embodiments, the immunoglobulin Fc region is selected from IgG or IgA. In certain embodiments, the immunoglobulin Fc region is selected from human IgG1, igG2, igG3 and/or IgG4 or an Fc region amino acid sequence having one or more amino acid mutations (preferably substitutions, insertions or deletions) with human IgG1, igG2, igG3, igG 4. In certain embodiments, the immunoglobulin comprises a chimeric antibody or antigen-binding fragment thereof, and/or a humanized antibody or antigen-binding fragment thereof. In certain embodiments, the immunoglobulin comprises an amino acid sequence as set forth in any one of SEQ ID NOs 9-13. The invention also provides a nucleic acid molecule encoding said single domain antibody or antigen binding fragment thereof or said immunoglobulin. The invention also provides a recombinant vector comprising the nucleic acid molecule. The invention also provides a recombinant cell comprising said nucleic acid molecule and/or said recombinant vector and capable of expressing said single domain antibody or antigen binding fragment thereof or said immunoglobulin. The invention also provides a pharmaceutical composition comprising the single domain antibody or antigen binding fragment thereof