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CN-122011187-A - Antibodies or antigen binding fragments thereof against porcine B cell surface CD19, compositions and uses thereof

CN122011187ACN 122011187 ACN122011187 ACN 122011187ACN-122011187-A

Abstract

The invention provides antibodies or antigen binding fragments thereof against porcine B cell surface CD19 and compositions and uses thereof. In particular, an anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof is provided that is capable of efficiently binding to CD19 on the surface of porcine B cells. The invention also provides antibody drug conjugates containing the antibody or antigen binding fragments thereof, and the like, which can be applied to screening of pig B cells and marking of CD19 antigens on the surfaces of the pig B cells, and have good application prospects.

Inventors

  • TONG PEI
  • WENG XIAOGANG
  • LIU ZHONGHUA
  • LI WANCHEN
  • DUAN XIAOYU

Assignees

  • 合肥综合性国家科学中心大健康研究院

Dates

Publication Date
20260512
Application Date
20250821

Claims (10)

  1. 1. An anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof has three complementarity determining HCDR regions of the heavy chain variable regions and three complementarity determining regions LCDR regions of the light chain variable regions: HCDR1 has an amino acid sequence shown as SEQ ID NO. 45, HCDR2 has an amino acid sequence as shown in SEQ ID NO. 46, HCDR3 has an amino acid sequence as shown in SEQ ID NO. 47; LCDR1 has an amino acid sequence as shown in SEQ ID NO. 64, LCDR2 having the amino acid sequence shown in SEQ ID NO. 50, and LCDR3 has an amino acid sequence as shown in SEQ ID NO. 51.
  2. 2. The antibody or antigen-binding fragment thereof of claim 1, wherein the heavy chain variable region and the light chain variable region of the anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof are a heavy chain variable region having the amino acid sequence shown in SEQ ID No. 62, and a light chain variable region having the amino acid sequence shown in SEQ ID No. 63.
  3. 3. A recombinant protein, wherein the recombinant protein has: (1) The anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof of claim 1, and (2) Optionally a tag sequence to assist expression and/or purification.
  4. 4. A polynucleotide expressing the anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof of claim 1.
  5. 5. A carrier, characterized in that, the vector contains the polynucleotide of claim 4.
  6. 6. A host cell expressing the anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof of claim 1, having the polynucleotide of claim 4 integrated into its genome, or comprising the vector of claim 5.
  7. 7. An antibody conjugate, characterized in that, the antibody conjugate comprises: (I) An antibody moiety comprising an anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof of claim 1, and (II) a coupling moiety coupled to the antibody or antigen binding fragment thereof, the coupling moiety being a detectable label.
  8. 8. A composition, characterized in that it comprises: (a) The anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof of claim 1, the recombinant protein of claim 2, the polynucleotide of claim 4, the vector of claim 5, the host cell of claim 6, or the antibody conjugate of claim 7, and (B) A pharmaceutically acceptable carrier.
  9. 9. Use of an anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof according to claim 1, a recombinant protein according to claim 3, a polynucleotide according to claim 4, a vector according to claim 5, a host cell according to claim 6, or an antibody conjugate according to claim 7 for the preparation of a detection reagent, a detection plate or a kit.
  10. 10. A method for non-diagnostic and non-therapeutic in vitro detection of CD19 protein in a sample, said method comprising the steps of: (y 1) contacting the sample with the antibody or antigen-binding fragment thereof of claim 1; (y 2) detecting whether an antigen-antibody complex is formed, wherein the formation of an antigen-antibody complex indicates the presence of CD19 protein in the sample.

Description

Antibodies or antigen binding fragments thereof against porcine B cell surface CD19, compositions and uses thereof Technical Field The invention belongs to the technical field of biology, and particularly relates to an antibody for resisting CD19 on the surface of a pig B cell or an antigen binding fragment thereof, and a composition and application thereof. Background Pigs are an ideal biomedical model for large animals, especially as models for the study of infectious diseases and vaccine development in humans, which are more similar to humans in terms of anatomy, physiology, genetics and immune response. The immune system of pigs is more than 80% of the analytical parameters similar to humans, whereas mice are only about 10%. The pig model can better simulate human diseases, and can verify the safety of medicines or the effectiveness of vaccines and the like before clinical trials. Differentiation of B lymphocytes into plasma cells following antigen stimulation to produce antibodies, either directly or indirectly, eliminates the pathogen, an important component of humoral immunity. CD19 is one of the first-discovered B lymphocyte surface markers, named B4 or Leu-12, and has the chemical property of transmembrane glycoprotein, and is a functional receptor molecule which starts to express from bone marrow progenitor B cells (Pro-B) and continues the whole maturation period of the B cells until the B cells differentiate into plasma cells and are widely distributed on the surfaces of the B lymphocytes. In addition, the main function of CD19 is to form a complex with CD21 and CD81, and when B cell receptor recognizes antigen, a B cell dual antigen binding model is formed, and the complex participates in the transportation of calcium ions in B cells to regulate the activation and proliferation of the B cells. Porcine CD19 is highly homologous to human and mouse CD19, with high homology to human, 73% for cytoplasmic domain, and relatively low (about 50%) for extracellular domain. This conservation suggests that its core function in signaling may be similar to human CD19, but species specificity also exists. However, the lack of monoclonal antibodies recognizing markers on the surface of pig cells brings great difficulty to pig model research and application. The research of monoclonal antibodies against pig CD19 has important significance for understanding key regulatory factors for pig B cell development, pig immune mechanism and developing novel vaccine and treatment method. Therefore, the monoclonal antibody against the porcine CD19 is urgently needed in the field, so that an effective tool is provided for researching the biological mechanism of porcine B cell development, and the monoclonal antibody has wide application prospects in the aspects of developing novel veterinary medicines, researching treatment methods and the like. Disclosure of Invention The invention aims to provide an antibody or antigen binding fragment thereof for resisting the surface CD19 of a pig B cell, and a composition and application thereof. In a first aspect of the invention there is provided an anti-porcine B cell surface CD19 antibody or antigen-binding fragment thereof having three complementarity determining HCDR of the heavy chain variable region and three complementarity determining regions LCDR of the light chain variable region: HCDR1 is X 1YX2FTDX3 E, wherein X 1 is selected from the group consisting of G or D, X 2 is selected from the group consisting of T or S, X 3 is selected from the group consisting of Y or F, HCDR2: IDPETGGX 4, wherein X 4 is selected from the group T, A or S, HCDR3: TRKQLWSYX 5FDX6, wherein X 5 is selected from the group consisting of Y or C, and X 6 is selected from the group consisting of Y or F; LCDR1 is EX 7VX8X9YGNX10 F, wherein X 7 is selected from the group consisting of S or N, X 8 is selected from the group consisting of D or A, X 9 is selected from the group consisting of S or N, X 10 is selected from the group consisting of S or R, LCDR2, LAS, and LCDR3:QQSNEDPYT。 In another preferred embodiment, the antibody or antigen binding fragment thereof has three complementarity determining HCDR regions of the heavy chain variable region and three complementarity determining regions LCDR regions of the light chain variable region: (A) The HCDR1 as shown in X 1YX2FTDX3 E wherein X 1、X2 and X 3 are selected from the group consisting of: (a1) X 1 is G, X 2 is S, and X 3 is Y; (a2) X 1 is G, X 2 is T, and X 3 is Y; (a3) X 1 is D, X 2 is T, X 3 is Y, or (A4) X 1 is G, X 2 is T, X 3 is F, The HCDR2 as depicted in IDPETGGX 4 wherein X 4 is selected from the group consisting of T, A and S, The HCDR3 of TRKQLWSYX 5FDX6 wherein X 5 and X 6 are selected from the group consisting of: (b1) X 5 is C, X 6 is Y, or (B2) X 5 is Y, X 6 is F; LCDR1 as shown in EX 7VX8X9YGNX10 F wherein X 7、X8、X9 and X 10 are selected from the group consisting of: (c1) X 7 is N, X 8 is A, X 9 is N, X 10 is R, or (C2) X 7 is S, X 8