1887

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Volume 102, Issue 7

Isolation and characterization of porcine monoclonal antibodies revealed two distinct serotype-independent epitopes on VP2 of foot-and-mouth disease virus No Access

Abstract

Pigs are susceptible to foot-and-mouth disease virus (FMDV), and the humoral immune response plays an essential role in protection against FMDV infection. However, little information is available about FMDV-specific mAbs derived from single B cells of pigs. This study aimed to determine the antigenic features of FMDV that are recognized by antibodies from pigs. Therefore, a panel of pig-derived mAbs against FMDV were developed using fluorescence-based single B cell antibody technology. Western blotting revealed that three of the antibodies (1C6, P2-7E and P2-8G) recognized conserved antigen epitopes on capsid protein VP2, and exhibited broad reactivity against both FMDV serotypes A and O. An alanine-substitution scanning assay and sequence conservation analysis elucidated that these porcine mAbs recognized two conserved epitopes on VP2: a linear epitope (KKTEETTLL) in the N terminus and a conformational epitope involving residues K63, H65, L66, F67, D68 and L81 on two β-sheets (B-sheet and C-sheet) that depended on the integrity of VP2. Random parings of heavy and light chains of the IgGs confirmed that the heavy chain is predominantly involved in binding to antigen. The light chain of porcine IgG contributes to the binding affinity toward an antigen and may function as a support platform for antibody stability. In summary, this study is the first to reveal the conserved antigenic profile of FMDV recognized by porcine B cells and provides a novel method for analysing the antibody response against FMDV in its natural hosts (i.e. pigs) at the clonal level.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): B cell , foot-and-mouth disease virus , monoclonal antibody , pig and universal epitope
Funding
This study was supported by the:
  • National Basic Research Program of China (973 Program) (Award Nos. 2017YFD0501104, and 2016YFD0501500)
    • Principle Award Recipient: ZaixinLiu
  • National Natural Science Foundation of China (Award 31902288)
    • Principle Award Recipient: KunLi
  • National Natural Science Foundation of China (Award 32072873)
    • Principle Award Recipient: YimeiCao
  • Key Research and Development Plan Project in Ningxia Province (Award 2019BBF02005)
    • Principle Award Recipient: PuSun
© 2021 The Authors
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/content/journal/jgv/10.1099/jgv.0.001608
2021-07-19
2024-05-05
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References

  1. Bachrach HL. Foot-and-mouth disease. Annu Rev Microbiol 1968; 22:201–244 [View Article] [PubMed]
     [Google Scholar]
  2. Grubman MJ, Baxt B. Foot-and-mouth disease. Clin Microbiol Rev 2004; 17:465–493 [View Article] [PubMed]
     [Google Scholar]
  3. Acharya R, Fry E, Stuart D, Fox G, Rowlands D et al. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature 1989; 337:709–716 [View Article] [PubMed]
     [Google Scholar]
  4. Morrell DJ, Mellor EJ, Rowlands DJ, Brown F. Surface structure and RNA-protein interactions of foot-and-mouth disease virus. J Gen Virol 1987; 68:1649–1658 [View Article]
     [Google Scholar]
  5. Crowther JR, Farias S, Carpenter WC, Samuel AR. Identification of a fifth neutralizable site on type O foot-and-mouth disease virus following characterization of single and quintuple monoclonal antibody escape mutants. J Gen Virol 1993; 74:1547–1553 [View Article]
     [Google Scholar]
  6. Kitson JD, McCahon D, Belsham GJ. Sequence analysis of monoclonal antibody resistant mutants of type O foot and mouth disease virus: evidence for the involvement of the three surface exposed capsid proteins in four antigenic sites. Virology 1990; 179:26–34 [View Article] [PubMed]
     [Google Scholar]
  7. McCahon D, Crowther JR, Belsham GJ, Kitson JD, Duchesne M et al. Evidence for at least four antigenic sites on type O foot-and-mouth disease virus involved in neutralization; identification by single and multiple site monoclonal antibody-resistant mutants. J Gen Virol 1989; 70:639–645 [View Article]
     [Google Scholar]
  8. Xie QC, McCahon D, Crowther JR, Belsham GJ, McCullough KC. Neutralization of foot-and-mouth disease virus can be mediated through any of at least three separate antigenic sites. J Gen Virol 1987; 68:1637–1647
     [Google Scholar]
  9. Ilyinskii PO, Roy CJ, O’Neil CP, Browning EA, Pittet LA et al. Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release. Vaccine 2014; 32:2882–2895 [View Article] [PubMed]
     [Google Scholar]
  10. Kim SM, Kim SK, Park JH, Lee KN, Ko YJ et al. A recombinant adenovirus bicistronically expressing porcine interferon-alpha and interferon-gamma enhances antiviral effects against foot-and-mouth disease virus. Antiviral Res 2014; 104:52–58 [View Article] [PubMed]
     [Google Scholar]
  11. Su J, Li J, Zheng H, You Y, Luo X et al. Adjuvant effects of L. acidophilus LW1 on immune responses to the foot-and-mouth disease virus DNA vaccine in mice. PloS one 2014; 9:e104446
     [Google Scholar]
  12. Yu W, Grubor-Bauk B, Gargett T, Garrod T, Gowans EJ. A novel challenge model to evaluate the efficacy of hepatitis C virus vaccines in mice. Vaccine 2014; 32:3409–3416 [View Article] [PubMed]
     [Google Scholar]
  13. Liu W, Yang B, Wang M, Liang W, Wang H et al. Identification of a conserved conformational epitope in the VP2 protein of foot-and-mouth disease virus. Arch Virol 2017; 162:1877–1885 [View Article] [PubMed]
     [Google Scholar]
  14. Butler JE, Sun J, Wertz N, Sinkora M. Antibody repertoire development in swine. Dev Comp Immunol 2006; 30:199–221 [View Article] [PubMed]
     [Google Scholar]
  15. Wang M, Pan L, Zhou P, Lv J, Zhang Z et al. Protection against foot-and-mouth disease virus in guinea pigs via oral administration of recombinant Lactobacillus plantarum expressing vp1. PloS one 2015; 10:e0143750
     [Google Scholar]
  16. Saravanan P, Sreenivasa BP, Selvan RP, Basagoudanavar SH, Hosamani M et al. Protective immune response to liposome adjuvanted high potency foot-and-mouth disease vaccine in Indian cattle. Vaccine 2015; 33:670–677 [View Article] [PubMed]
     [Google Scholar]
  17. Rodriguez-Gomez IM, Kaser T, Gomez-Laguna J, Lamp B, Sinn L et al. PRRSV-infected monocyte-derived dendritic cells express high levels of SLA-DR and CD80/86 but do not stimulate PRRSV-naive regulatory T cells to proliferate. Vet Res 2015; 46:54 [View Article] [PubMed]
     [Google Scholar]
  18. Chan YK, Gack MU. RIG-I-like receptor regulation in virus infection and immunity. Curr Opin Virol 2015; 12:7–14 [View Article] [PubMed]
     [Google Scholar]
  19. Habiela M, Seago J, Perez-Martin E, Waters R, Windsor M et al. Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity. J Gen Virol 2014; 95:2329–2345 [View Article] [PubMed]
     [Google Scholar]
  20. Liang T, Yang D, Liu M, Sun C, Wang F et al. Selection and characterization of an acid-resistant mutant of serotype O foot-and-mouth disease virus. Arch Virol 2014; 159:657–667 [View Article] [PubMed]
     [Google Scholar]
  21. Xu J, Guo HC, Wei YQ, Dong H, Han SC et al. Self-assembly of virus-like particles of canine parvovirus capsid protein expressed from Escherichia coli and application as virus-like particle vaccine. Appl Microbiol Biotechnol 2014; 98:3529–3538 [View Article] [PubMed]
     [Google Scholar]
  22. Ding YZ, Chen HT, Zhang J, Zhou JH, Ma LN et al. An overview of control strategy and diagnostic technology for foot-and-mouth disease in China. Virol J 2013; 10:78 [View Article] [PubMed]
     [Google Scholar]
  23. Spieker-Polet H, Sethupathi P, Yam PC, Knight KL. Rabbit monoclonal antibodies: generating a fusion partner to produce rabbit-rabbit hybridomas. Proc Natl Acad Sci USA 1995; 92:9348–9352 [View Article] [PubMed]
     [Google Scholar]
  24. Ren J, Nettleship JE, Harris G, Mwangi W, Rhaman N et al. The role of the light chain in the structure and binding activity of two cattle antibodies that neutralize bovine respiratory syncytial virus. Mol Immunol 2019; 112:123–130 [View Article] [PubMed]
     [Google Scholar]
  25. Xiao H, Guo T, Yang M, Qi J, Huang C et al. Light chain modulates heavy chain conformation to change protection profile of monoclonal antibodies against influenza A viruses. Cell Discov 2019; 5:21 [View Article] [PubMed]
     [Google Scholar]
  26. Wang M, Gao Z, Pan L, Zhang Y. Cellular microRNAs and picornaviral infections. RNA Biol 2014; 11:808–816 [View Article] [PubMed]
     [Google Scholar]
  27. Fang M, Wang H, Tang T, Zhao P, Du J et al. Single immunization with a recombinant multiple-epitope protein induced protection against FMDV type Asia 1 in cattle. Int Immunopharmacol 2015; 28:960–966 [View Article] [PubMed]
     [Google Scholar]
  28. Azuma M, Takeda Y, Nakajima H, Sugiyama H, Ebihara T et al. Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy. Oncoimmunology 2016; 5:e1188244 [View Article] [PubMed]
     [Google Scholar]
  29. Borrego B, Rodríguez-Pulido M, Revilla C, Álvarez B, Sobrino F et al. Synthetic RNAs mimicking structural domains in the Foot-and-Mouth disease virus genome elicit a broad innate immune response in porcine cells triggered by RIG-I and TLR activation. Viruses 2015; 7:3954–3973 [View Article] [PubMed]
     [Google Scholar]
  30. Orgad R, Nathansohn-Levi B, Kagan S, Reisner Y. Novel immunoregulatory role of perforin-positive dendritic cells. Semin Immunopathol 2016; 30:30
     [Google Scholar]
  31. Brito BP, Perez AM, Capozzo AV. Accuracy of traditional and novel serology tests for predicting cross-protection in foot-and-mouth disease vaccinated cattle. Vaccine 2014; 32:433–436 [View Article] [PubMed]
     [Google Scholar]
  32. Elnekave E, Shilo H, Gelman B, Klement E. The longevity of anti NSP antibodies and the sensitivity of a 3ABC ELISA - A 3 years follow up of repeatedly vaccinated dairy cattle infected by foot and mouth disease virus. Vet Microbiol 2015; 178:14–18 [View Article] [PubMed]
     [Google Scholar]
  33. Eduardo S. Rearrangement of only one human IGHV gene is sufficient to generate a wide repertoire of antigen specific antibody responses in transgenic mice. Mol Immunol 2006; 11:
     [Google Scholar]
  34. Joyce M, Wheatley A, Thomas P, Chuang G, Soto C et al. Vaccine-induced antibodies that neutralize group 1 and group 2 Influenza A viruses. Cell 2016; 166:609–623 [View Article] [PubMed]
     [Google Scholar]
  35. Radic M, Mascelli M, Erikson J, Shan H, Weigert M. Ig H and L chain contributions to autoimmune specificities. J Immunol 1991; 146:176–182 [PubMed]
     [Google Scholar]
  36. Wiehe K, Easterhoff D, Luo K, Nicely N, Bradley T et al. Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved. Immunity 2014; 41:909–918 [View Article] [PubMed]
     [Google Scholar]
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Isolation and characterization of porcine monoclonal antibodies revealed two distinct serotype-independent epitopes on VP2 of foot-and-mouth disease virus
J. Gen. Virol. 102, 001608 (2021); https://doi.org/10.1099/jgv.0.001608
/content/journal/jgv/10.1099/jgv.0.001608
/content/journal/jgv/10.1099/jgv.0.001608
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