Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage
Cattle are susceptible to foot-and-mouth disease virus (FMDV), and neutralizing antibodies are critical for protection against FMDV infection in this species. However, more information is needed on the host specific antigenic structure recognized by the FMDV-specific monoclonal antibodies (mAbs) and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02870/full |
| _version_ | 1818514226306613248 |
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| author | Kun Li Sheng Wang Yimei Cao Huifang Bao Pinghua Li Pu Sun Xingwen Bai Yuanfang Fu Xueqing Ma Jing Zhang Dong Li Yingli Chen Xuerong Liu Fanglan An Faju Wu Zengjun Lu Zaixin Liu |
| author_facet | Kun Li Sheng Wang Yimei Cao Huifang Bao Pinghua Li Pu Sun Xingwen Bai Yuanfang Fu Xueqing Ma Jing Zhang Dong Li Yingli Chen Xuerong Liu Fanglan An Faju Wu Zengjun Lu Zaixin Liu |
| author_sort | Kun Li |
| collection | DOAJ |
| description | Cattle are susceptible to foot-and-mouth disease virus (FMDV), and neutralizing antibodies are critical for protection against FMDV infection in this species. However, more information is needed on the host specific antigenic structure recognized by the FMDV-specific monoclonal antibodies (mAbs) and on the functional properties of the mAb that are produced in the natural host, cattle. Herein, we characterized 55 plasmablast-derived mAbs from three FMDV-infected cattle and obtained 28 FMDV-neutralizing antibodies by the single B cell antibody technique. The neutralizing mAbs (27/28) mainly recognized conformational epitopes that differ from the well-characterized immunodominant antigenic site 1 of FMDV as defined by murine mAbs. Of these FMDV-neutralizing mAbs, 13 mAbs showed intra-type broadly neutralizing activity against the three topotypes of FMDV serotype O (ME-SA, SEA, and Cathay topotypes). Moreover, all these intra-type broadly neutralizing antibodies competed with sera from FMDV infected or vaccinated cattle, which indicates their binding to native dominant epitopes, as revealed by a blocking ELISA. We further analyzed the germline V(D)J gene usage of the 55 FMDV-specific mAbs and found cattle IgG antibodies containing ultralong HCDR3 were exclusively restricted to usage of the germline gene segment VH 1-7*02. In addition, the restricted germline gene segments of VH 1-7*02 and VL1-47*01 or 1-52*01 pairing were observed in all IgG antibodies with ultralong HCDR3. Furthermore, antibodies with longer HCDR3 were more inclined to display FMDV-neutralizing activity. This study presents a novel method for screening FMDV-specific cattle mAbs which then provide the most useful tools for studying FMDV antigenic structure and variation. |
| first_indexed | 2024-12-11T00:12:52Z |
| format | Article |
| id | doaj.art-ac674c8c8d524d61a1185a512483cf23 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T00:12:52Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ac674c8c8d524d61a1185a512483cf232022-12-22T01:28:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-12-011010.3389/fimmu.2019.02870464959Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene UsageKun Li0Sheng Wang1Yimei Cao2Huifang Bao3Pinghua Li4Pu Sun5Xingwen Bai6Yuanfang Fu7Xueqing Ma8Jing Zhang9Dong Li10Yingli Chen11Xuerong Liu12Fanglan An13Faju Wu14Zengjun Lu15Zaixin Liu16State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaChina Agricultural Vet Biology and Technology Co. Ltd., Lanzhou, ChinaChina Agricultural Vet Biology and Technology Co. Ltd., Lanzhou, ChinaChina Agricultural Vet Biology and Technology Co. Ltd., Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaCattle are susceptible to foot-and-mouth disease virus (FMDV), and neutralizing antibodies are critical for protection against FMDV infection in this species. However, more information is needed on the host specific antigenic structure recognized by the FMDV-specific monoclonal antibodies (mAbs) and on the functional properties of the mAb that are produced in the natural host, cattle. Herein, we characterized 55 plasmablast-derived mAbs from three FMDV-infected cattle and obtained 28 FMDV-neutralizing antibodies by the single B cell antibody technique. The neutralizing mAbs (27/28) mainly recognized conformational epitopes that differ from the well-characterized immunodominant antigenic site 1 of FMDV as defined by murine mAbs. Of these FMDV-neutralizing mAbs, 13 mAbs showed intra-type broadly neutralizing activity against the three topotypes of FMDV serotype O (ME-SA, SEA, and Cathay topotypes). Moreover, all these intra-type broadly neutralizing antibodies competed with sera from FMDV infected or vaccinated cattle, which indicates their binding to native dominant epitopes, as revealed by a blocking ELISA. We further analyzed the germline V(D)J gene usage of the 55 FMDV-specific mAbs and found cattle IgG antibodies containing ultralong HCDR3 were exclusively restricted to usage of the germline gene segment VH 1-7*02. In addition, the restricted germline gene segments of VH 1-7*02 and VL1-47*01 or 1-52*01 pairing were observed in all IgG antibodies with ultralong HCDR3. Furthermore, antibodies with longer HCDR3 were more inclined to display FMDV-neutralizing activity. This study presents a novel method for screening FMDV-specific cattle mAbs which then provide the most useful tools for studying FMDV antigenic structure and variation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02870/fullcattlefoot-and-mouth disease virusbroadly neutralizing antibodiesantigenic charactersingle B cell antibody |
| spellingShingle | Kun Li Sheng Wang Yimei Cao Huifang Bao Pinghua Li Pu Sun Xingwen Bai Yuanfang Fu Xueqing Ma Jing Zhang Dong Li Yingli Chen Xuerong Liu Fanglan An Faju Wu Zengjun Lu Zaixin Liu Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage Frontiers in Immunology cattle foot-and-mouth disease virus broadly neutralizing antibodies antigenic character single B cell antibody |
| title | Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage |
| title_full | Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage |
| title_fullStr | Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage |
| title_full_unstemmed | Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage |
| title_short | Development of Foot-and-Mouth Disease Virus-Neutralizing Monoclonal Antibodies Derived From Plasmablasts of Infected Cattle and Their Germline Gene Usage |
| title_sort | development of foot and mouth disease virus neutralizing monoclonal antibodies derived from plasmablasts of infected cattle and their germline gene usage |
| topic | cattle foot-and-mouth disease virus broadly neutralizing antibodies antigenic character single B cell antibody |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02870/full |
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