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CN-122011173-A - Foot-and-mouth disease virus type O specific neutralizing swine monoclonal antibody and application thereof

CN122011173ACN 122011173 ACN122011173 ACN 122011173ACN-122011173-A

Abstract

The invention discloses foot-and-mouth disease virus type O neutralizing swine monoclonal antibodies pO18-40 and pO18-43. The amino acid sequences of the heavy chain variable region (VH) and the light chain variable region (VL) of the antibody pO18-40 are shown as SEQ ID No. 1 and SEQ ID No. 2, respectively, and the amino acid sequences of the VH and the VL of the antibody pO18-43 are shown as SEQ ID No.3 and SEQ ID No. 4, respectively. The antibody obtained by the invention is a whole pig source antibody, can specifically neutralize the classical strain of the O-type foot-and-mouth disease virus, and can clearly distinguish the classical strain and the variant strain of the O/Cathay topology type. The key epitope identified by the antibody is positioned at the 149 th amino acid of the G-H loop of VP1 protein, and the site is the key site for O/Cathay strain antigen variation and vaccine immune protection. The antibody provided by the invention provides an important tool and theoretical basis for serological detection of O-type FMDV, vaccine immune effect evaluation and optimization design of broad-spectrum vaccine.

Inventors

  • LI FENGJUAN
  • FU YUANFANG
  • YUAN HONG
  • MA XUEQING
  • LI JIAOYANG
  • LI DONG
  • ZHAO ZHIXUN
  • ZHANG JING
  • WANG JIAN
  • ZHANG QIANG
  • LU ZENGJUN
  • LI KUN
  • Cao Diemei
  • BAO HUIFANG
  • LI PINGHUA
  • SUN PU
  • BAI XINGWEN
  • Huang Shulun

Assignees

  • 中国农业科学院兰州兽医研究所(中国动物卫生与流行病学中心兰州分中心)

Dates

Publication Date
20260512
Application Date
20260211

Claims (7)

  1. 1. A foot-and-mouth disease virus type O neutralizing swine monoclonal antibody pO18-40 is characterized in that the amino acid sequence of a heavy chain variable region of the monoclonal antibody pO18-40 is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region is shown as SEQ ID No. 2.
  2. 2. A foot-and-mouth disease virus type O neutralizing swine monoclonal antibody pO18-43 is characterized in that the amino acid sequence of a heavy chain variable region of the monoclonal antibody pO18-43 is shown as SEQ ID No.3, and the amino acid sequence of a light chain variable region is shown as SEQ ID No. 4.
  3. 3. An antibody composition for detecting foot-and-mouth disease virus type O, comprising the monoclonal antibody pO18-40 of claim 1 and/or the monoclonal antibody pO18-43 of claim 2.
  4. 4. Use of the monoclonal antibody pO18-40 of claim 1, the monoclonal antibody pO18-43 of claim 2 or the antibody composition of claim 3 for the preparation of a kit or a kit for detecting foot-and-mouth disease virus type O.
  5. 5. The use according to claim 4, wherein the detection reagent or kit is used for identifying classical foot-and-mouth disease strains of the O/Cathay lineage and variant foot-and-mouth disease strains of the O/Cathay lineage.
  6. 6. The use according to claim 4, wherein the detection reagent or kit is for detecting foot-and-mouth disease virus type O by recognizing amino acid VP1 position 149 of the G-H loop region of foot-and-mouth disease virus VP1 protein.
  7. 7. Use of the monoclonal antibody pO18-40 of claim 1 or the monoclonal antibody pO18-43 of claim 2 for screening or optimally designing broad-spectrum vaccine strains of foot-and-mouth disease virus type O.

Description

Foot-and-mouth disease virus type O specific neutralizing swine monoclonal antibody and application thereof Technical Field The invention belongs to the technical field of biology, and relates to a foot-and-mouth disease virus O-type neutralizing swine monoclonal antibody and application thereof. Background Foot-and-mouth disease (FMD) is a virulent infectious disease causing the disease of artiodactyls such as pigs, cattle and sheep by Foot-and-mouth disease virus (FMDV). The world animal health organization (WOAH) lists it as a legally reported animal epidemic, and China lists it as a major animal epidemic with priority control. FMDV comprises 7 serotypes, of which FMDV type O is most widely distributed, 11 topologically prevalent worldwide, and easily mutated and difficult to control effectively. Currently, type O FMDV is the most serious serotype jeopardizing the livestock breeding industry in China, and 3 topological type 4 lineage strains (Cathay, ME-SA/PanAlsia, ME-SA/Ind-2001 and SEA/Mya 98) are mixed and popular in recent years. Recent research reports show that the genetic diversity of SEA and ME-SA topological viruses has a decreasing trend, the evolution rate of Cathay topological strains is accelerated, and the genetic diversity is greatly increased in the last ten years, so that the spreading popularity of Cathay topological strains in Asia areas shows an expanding development situation. Particularly, the matching property of the O/Cathay variant strain and the existing O-type vaccine strain is obviously reduced, which suggests that structural variation occurs in key antigen sites of the topological variant strain, but the molecular basis of the structural variation of the antigen is not clear at present, so that the research and development and optimization of the O-type broad-spectrum vaccine lack theoretical support, and the accurate prevention and control of the O-type foot-and-mouth disease cannot be realized. Meanwhile, the existing foot-and-mouth disease virus detection reagent is prepared by a plurality of non-natural host source antibodies, has low matching degree with the immune response characteristics of a natural host, is difficult to accurately distinguish classical strains from variant strains, and has the detection specificity and sensitivity to be improved. Disclosure of Invention The invention aims to provide monoclonal antibodies pO18-40 and pO18-43 of foot-and-mouth disease virus type O neutralizing porcine sources, which are natural host porcine sources, can specifically identify key antigenic sites of type O FMDV, have good neutralizing activity on classical strains, and can clearly distinguish classical strains from variant strains. The invention also aims to provide application of the swine monoclonal antibody, and provides a new tool and theoretical basis for detection of O-type foot-and-mouth disease virus, screening and optimization design of vaccine strains, so that precise prevention and control of foot-and-mouth disease are realized. In order to achieve the above purpose, the present invention adopts the following technical scheme: the invention provides a foot-and-mouth disease virus type O neutralizing swine monoclonal antibody pO18-40, wherein the amino acid sequence of a heavy chain variable region is shown as SEQ ID No.1, and the amino acid sequence of a light chain variable region is shown as SEQ ID No. 2. PO18-40 heavy chain variable region (SEQ ID No. 1): EEKVVESGGGQVRPGESLRLSCLAEGVTFSRHSVRWVRQSPGKGLEFVIYMFNAVDSVDIADYVKGRFTVSRDNAQNTAYLQMTKLRVEDTGRYFCLIGNKWFGPGVEVVVSS; pO18-40 light chain variable region (SEQ ID No. 2): AIVLTQSPLYLSVTPGEPASISCKSTKSVLDTDGTTVLNWYLQKPGQAPQRVIWSAIYRETGVPDRFTGSGSGTDFTLYISRVEAEDVGVYYCQQSRESTSFGAGTKLDLK. The invention also provides a foot-and-mouth disease virus type O neutralizing swine monoclonal antibody pO18-43, wherein the amino acid sequence of a heavy chain variable region is shown as SEQ ID No.3, and the amino acid sequence of a light chain variable region is shown as SEQ ID No. 4. PO18-43 heavy chain variable region (SEQ ID No. 3): EEKVVESGGGLVQPGGSLRLSCVGSGYMFSKYGMTWVRHSQRKGLEWLAGIDNFESTDYAASVKGRFTLWRDNSQNTAYLEMSFLGVEDTARYYCGRGFGVPYIWGPGVEVVVSS; pO18-43 light chain variable region (SEQ ID No. 4): AVELTQTPVSLSVSPGEPASISCRSSQSLLHSDGRNYLTWYRIKPGQSPQRLVYYGTYRDPEIPDRFTGSESGTDFTLKISRVEAEDAGVYYCLQSKEPPYEFGAGTNLDLK. The monoclonal antibodies pO18-40 and pO18-43 are O-type FMDV specific neutralizing antibodies, have good neutralizing activity (IC 50 is less than or equal to 50 mug.mL-1) and binding capacity on O/Cathay lineages classical strain O/HN/CHA/93 and O type PanAsia lineages strain O/Xizang/99 and Mya lineages strain O/GSLX/2010, and have no neutralizing activity (IC 50 is more than 50 mug.mL-1) and binding activity on O/Cathay topological variant strains (including O/SCGH/CHA/2016, O/18074, O/GD/2021 and O/GX/2022), so that antigen differences of the O/Cathay lineages classical strain and variant strain can be clearly d