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CN-121991215-A - Humanized anti-respiratory syncytial virus neutralizing antibody RS414 and application thereof

CN121991215ACN 121991215 ACN121991215 ACN 121991215ACN-121991215-A

Abstract

The invention discloses a humanized anti-respiratory syncytial virus neutralizing antibody RS414 and application thereof. Antibody RS414 was obtained by screening using phage surface display technology. The antibody specifically recognizes respiratory syncytial virus particle antigen, is directed against respiratory syncytial virus F protein, has obvious enzyme-linked immune reaction with respiratory syncytial virus, and has the neutralizing activity function of resisting respiratory syncytial virus infection. The antibody of the invention can be prepared into specific antibody medicines for preventing and treating respiratory syncytial virus infection, and can clinically prevent or treat lower respiratory tract infection caused by respiratory syncytial virus, especially serious lower respiratory tract infection (pneumonia and bronchiolitis).

Inventors

  • WU WEI
  • LIANG MIFANG
  • WANG MENGXUAN
  • HUANG FANG
  • LI BOYANG
  • JIANG YONG

Assignees

  • 武汉江源新抗生物科技有限公司

Dates

Publication Date
20260508
Application Date
20260228

Claims (10)

  1. 1. A human anti-respiratory syncytial virus neutralizing antibody RS414 or an active fragment thereof, wherein the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the light chain variable region of the antibody or active fragment thereof are SSNIGAGYD, VNN, QSYDSSLGGSI, respectively, and the amino acid sequences of complementarity determining regions CDR1, CDR2, CDR3 of the heavy chain variable region are GFRTSGYY, ISAGSSYI, ARVKPGTYGDYYDY, respectively.
  2. 2. The antibody or active fragment thereof according to claim 1, wherein the amino acid sequence of the light chain variable region of the antibody or active fragment thereof is shown in SEQ ID No.1 and the amino acid sequence of the heavy chain variable region is shown in SEQ ID No. 2.
  3. 3. The antibody or active fragment thereof according to claim 1 or 2, wherein said active fragment is selected from the group consisting of Fab ', fab, F (ab') 2, fv and scFv fragments.
  4. 4. A nucleic acid molecule encoding the antibody or active fragment thereof of any one of claims 1-3.
  5. 5. A biological material comprising the nucleic acid molecule of claim 4, wherein the biological material is an expression cassette, a transposon, a plasmid vector, a viral vector or an engineering bacterium.
  6. 6. Use of an antibody or active fragment thereof according to any one of claims 1-3 for the preparation of a medicament or diagnostic agent for the prevention or treatment of respiratory syncytial virus infection.
  7. 7. Use of an antibody or active fragment thereof according to any one of claims 1-3 for the preparation of a medicament or composition for the prevention or treatment of lower respiratory tract infections caused by respiratory syncytial virus.
  8. 8. A medicament for preventing or treating respiratory syncytial virus infection, characterized in that the antibody or an active fragment thereof according to any one of claims 1-3 is an active ingredient.
  9. 9. A medicament for preventing or treating lower respiratory tract infection caused by respiratory syncytial virus, characterized in that the antibody or an active fragment thereof according to any one of claims 1-3 is used as an active ingredient.
  10. 10. The medicament according to claim 8 or 9, further comprising pharmaceutical excipients.

Description

Humanized anti-respiratory syncytial virus neutralizing antibody RS414 and application thereof Technical Field The invention relates to the technical field of genetic engineering antibodies, in particular to a humanized anti-respiratory syncytial virus neutralizing antibody RS414 and application thereof. Background Respiratory Syncytial Virus (RSV) is the most important causative agent of lower respiratory tract infections, especially severe lower respiratory tract infections (pneumonia, bronchiolitis), in infants and young children worldwide and in our country, and is also a major risk factor for respiratory tract infections in immunosuppressed patients and the elderly. Infants may be infected by exposure to RSV shortly after birth, at least 2 weeks are required to complete the full-length vaccine active immunization protection, the infant immune system is still immature, the immune response of vaccination is relatively weak, and RSV vaccine is not suitable for infants under 6 months of age. Thus, monoclonal antibodies have been explored for passive immunoprotection strategies to prevent RSV infection in infants. The F protein (Fusion protein) of Respiratory Syncytial Virus (RSV) is a critical glycoprotein on the viral surface and plays a critical role in the viral infection process. The F protein is exposed on the surface of the virus in the form of homotrimers and is the main mediator of fusion of the virus with the host cell membrane. The F protein is initially synthesized in the inactive precursor form (F0) and, upon cleavage by the host cell protease, produces two disulfide-linked subunits F1 and F2, which together constitute the mature F protein with fusion capability. Functionally, the active F protein is in a metastable "pre-fusion" (pre-F) state until a triggering event induces a conformational change thereof, exposing the fusion peptide and inserting into the target membrane, followed by the formation of a six-helix bundle, driving the completion of the membrane fusion process. The two main conformational states of the F protein, pre-fusion conformation (pre-F) and post-fusion conformation (post-F), have different immunological properties. Studies have shown that the pre-F conformation is more immunogenic than the post-F conformation and is capable of inducing the production of more efficient neutralizing antibodies. This difference is mainly due to the fact that the exposed and V epitopes are the strongest neutralizing antibody epitopes of the F protein in the pre-F state, whereas these epitopes are blocked in the post-F state. The RSV fusion protein (F protein) has high conservation, and is a hot spot protein for developing antibodies, vaccines and other therapeutic medicaments. Panivizumab (Palivizumab) was approved by the FDA in 1998, and the first short-acting monoclonal antibody against the RSV F protein was marketed for the prevention of lower respiratory tract infection in infants and infants with severe RSV disease, and was approved in europe and america for high risk infants with severe RSV disease with underlying disease. The panizumab has short half-life period, but needs to be injected once a month and has high cost, thus limiting the wide application range. The long-acting monoclonal antibody drug nisi Wei Shankang (Nirsevimab), which was co-operated with celecoxib in 2024, was approved in china as the first and only drug for preventing RSV lower respiratory tract infection in newborns and infants. The medicine can cover the whole RSV infection season through single injection, and clinical data show that the protection effect of the medicine on RSV related lower respiratory tract infection reaches 78.4%, and the hospitalization rate is reduced by 44.4%. Long-acting monoclonal antibody Clesrovimab (MK-1654) developed by moesadong is in the research stage and can be injected intramuscularly at a single fixed dose (105 mg) and is suitable for use in healthy premature infants and term infants. The critical IIb/III phase experiment shows that the effectiveness of preventing the RSV lower respiratory tract infection requiring medical intervention is 60.4%, and the hospitalization rate is reduced by 84% -90%. The U.S. FDA approval was obtained on day 6 and 10 of 2025, and the national drug administration was accepted by the national drug administration for inclusion priority rating on its market. In addition to breaking through the application limitation of short half-life, the new generation of antibody drugs reduces the use threshold by simplifying the dosing regimen compared to palivizumab. Human or animal serum immunoglobulins containing specific antibodies have long been used to prevent and treat infectious diseases. In vitro antiviral neutralizing activity and in vivo protection of monoclonal antibodies against viral challenge many experiments have been obtained to demonstrate that neutralizing monoclonal antibodies such as murine anti-hepatitis a virus, hantavirus, measles virus, RS