Detection of antibodies to non-structural proteins of foot-and-mouth disease virus (review)

Foot-and-mouth disease (FMD) isa highlycontagiousviraldiseaseof cloven-hoovedanimals that can causeepidemicsandgreateconomic losses. Thedisease remains a huge problem in developing countries and poses a constant threat to developed countries. Detection of antibodies to FMD virus non-structural proteins in thebloodof susceptibleanimals isan important tool for thediseasecontrol. This is theonly way for reliabledifferentiation of vaccinatedanimals fromconvalescentandvirus-carrieranimals. Variousmodificationsof solid-phaseenzymeimmunosorbentassay (ELISA) havebeen developedfordetection of antibodies toFMD virus nonstructuralproteins. RecombinantFMD virus non-structuralproteins, mostly 3АВС or 3АВ, areusedasan antigen for such assay. In ashort time, recombinant FMD virusantigen-basedELISA hasevolvedfrom an in-houselaboratory methodtocommonlyavailablecommercial test systems, mostof which have high diagnostic specificityandsensitivity. Thesaid methodis widelyusedforFMD surveillance. In thecountriesandzones freefrom FMD withoutvaccination theELISA fordetection ofantibodiesagainstFMD virus non-structuralproteinsisusedasaprimarymethodforFMD serologicalmonitoring andretrospectivediagnosis. In thecountriesandzones freefromFMD with vaccination thisELISA isusedforconfirmation of thevirus infection absencein vaccinated herds. In South America, ELISA fordetection ofantibodiesagainstFMD virus non-structuralproteins wasusedfordetection of infectedanimalsduring thediseaseeradication. Currently, it isusedfor monitoringfor thevirus circulation in stillFMD infected Asian and African countries implementingprogressive FMD controlprogramme. In Russia havingzones where anti-FMD vaccination is carriedout this methodis a mandatory tool of thedisease surveillance. The review isbasedon theanalysisof 65 publications.

1. Jamal S. M., Belsham G. J. Foot-and-mouth disease: past, present and future. Vet. Res. 2013; 44 (1):116. DOI: 10.1186/1297-9716-44-116.

2. Grubman M. J., Baxt B. Foot-and-mouth disease. Clin. Microbiol. Rev. 2004; 17 (2): 465–493. DOI: 10.1128/CMR.17.2.465-493.2004.

3. Samuel A. R., Knowles N. J. Foot-and-mouth disease type O viruses exhibit genetically and geographically distinct evolutionary lineages (topotypes). J. Gen. Virol. 2001; 82 (3): 609–621. DOI: 10.1099/0022-1317-82-3-609.

4. Carrillo C., Tulman E. R., Delhon G., Lu Z., Carreno A., Vagnozzi A., et al. Comparative genomics of foot-and-mouth disease virus. J. Virol. 2005; 79 (10): 6487–6504. DOI: 10.1128/JVI.79.10.6487-6504.2005.

5. Hutber A. M., Kitching R. P., Conway D. A. Control of foot-and-mouth disease through vaccination and the isolation of infected animals. Trop. Anim. Health. Prod. 1998; 30 (4): 217–227. DOI: 10.1023/a:1005071027414.

6. Arzt J., Belsham G. J., Lohse L., Bøtner A., Stenfeldt C. Transmission of foot-and-mouth disease from persistently infected carrier cattle to naive cattle via transfer of oropharyngeal fluid. mSphere. 2018; 3 (5):e00365–18. DOI: 10.1128/mSphere.00365-18.

7. Crowther J. R. Review of the developments in the detection of antibodies to non-structural proteins of foot and mouth disease virus. In: The use of non-structural proteins of foot and mouth disease virus (FMDV) to differentiate between vaccinated and infected animals. Vienna: IAEA; 2007; 3–46. Режим доступа: https://www-pub.iaea.org/MTCD/publications/PDF/ te_1546_web.pdf. (дата обращения: 18.01.2023).

8. Tewari A., Ambrose H., Parekh K., Inoue T., Guitian J., Nardo A. D., et al. Development and validation of confirmatory foot-and-mouth disease virus antibody ELISAsto identify infected animalsin vaccinated populations. Viruses. 2021; 13 (5):914. DOI: 10.3390/v13050914.

9. Clavijo A., Wright P., Kitching P. Developments in diagnostic techniques for differentiating infection from vaccination in foot-and-mouth disease. Vet. J. 2004; 167 (1): 9–22. DOI: 10.1016/s1090-0233(03)00087-x.

10. Yadin H., Brenner J., Chai D., Oved Z., Hadany Y., Kusak A., Haimovich M. The NSP immune response of vaccinated animals after in-field exposure to FMDV. Vaccine. 2007; 25 (49): 8298–8305. DOI: 10.1016/j.vaccine.2007.09.071.

11. GaoY., Sun S. Q., GuoH. C. Biological function of foot-and-mouth disease virus non-structural proteins and non-coding elements. Virol. J. 2016; 13:107. DOI: 10.1186/s12985-016-0561-z.

12. Doel T. R. FMD vaccines. Virus Res. 2003; 91 (1): 81–99. DOI: 10.1016/ s0168-1702(02)00261-7.

13. Lubroth J., Grubman M. J., Burrage T. G., Newman J. F., Brown F. Absence of protein 2C from clarified foot-and-mouth disease virus vaccines providesthe basisfor distinguishing convalescentfrom vaccinated animals. Vaccine. 1996; 14 (5): 419–427. DOI: 10.1016/0264-410x(95)00172-w.

14. McVicar J. W., Sutmoller P. Foot-and-mouth disease: the agar gel diffusion precipitin testfor antibody to virus-infection-associated (via) antigen as a tool for epizootiologic surveys. Am. J. Epidemiol. 1970; 92 (4): 273–278. DOI: 10.1093/oxfordjournals.aje.a121207.

15. Bergmann I. E., de Mello P. A., Neitzert E., Beck E., GomesI. Diagnosis of persistent aphthovirusinfection and its differentiation from vaccination response in cattle by use of enzyme-linked immunoelectrotransfer blot analysis with bioengineered nonstructural viral antigens. Am. J. Vet. Res. 1993; 54 (6): 825–831. PMID: 8391765.

16. Ma L. N., Zhang J., Chen H. T., Zhou J. H., Ding Y. Z., Liu Y. S. An overview on ELISA techniques for FMD. Virol. J. 2011; 8:419. DOI: 10.1186/1743- 422X-8-419.

17. Shen F., Chen P. D., Walfield A. M., Ye J., House J., Brown F., Wang C. Y. Differentiation of convalescent animals from those vaccinated against foot-and-mouth disease by a peptide ELISA. Vaccine. 1999; 17 (23–24): 3039–3049. DOI: 10.1016/s0264-410x(99)00148-6.

18. Oem J. K., Kye S. J., Lee K. N., Park J. H., Kim Y. J., Song H. J., Yeh M. Development of synthetic peptide ELISA based on nonstructural protein 2C of foot and mouth disease virus. J. Vet. Sci. 2005; 6 (4): 317–325. PMID: 16293996.

19. Crowther J. R. The use of non-structural (NS) antigens of FMD virus to assess antibodies in vaccinanted and infected livestock. In: Foot-andmouth disease: control strategies. Symposium Proceedings (2–5 June 2002). Lyons, France: 2002; 377.

20. Rodríguez A., Dopazo J., Sáiz J. C., Sobrino F. Immunogenicity of non-structural proteins of foot-and-mouth disease virus: differences between infected and vaccinated swine. Arch. Virol. 1994; 136 (1–2): 123–131. DOI: 10.1007/BF01538822.

21. De Diego M., Brocchi E., Mackay D., De Simone F. The non-structural polyprotein 3ABC of foot-and-mouth disease virus as a diagnostic antigen in ELISA to differentiate infected from vaccinated cattle. Arch. Virol. 1997; 142 (10): 2021–2033. DOI: 10.1007/s007050050219.

22. Foster M., Cook A., Cedillo L., Parkhouse R. M. Serological and cellular immune responses to non-structural proteins in animals infected with FMDV. Vet. Q. 1998; 20 (Suppl. 2): S28–30. DOI: 10.1080/01652176.1998. 9694960.

23. Mackay D. K., Forsyth M. A., Davies P. R., Berlinzani A., Belsham G. J., Flint M., Ryan M. D. Differentiating infection from vaccination in foot-andmouth disease using a panel of recombinant, non-structural proteins in ELISA. Vaccine. 1998; 16 (5): 446–459. DOI: 10.1016/s0264-410x(97)00227-2.

24. Sørensen K. J., de Stricker K., Dyrting K. C., Grazioli S., Haas B. Differentiation of foot-and-mouth disease virus infected animals from vaccinated animals using a blocking ELISA based on baculovirus expressed FMDV 3ABC antigen and a 3ABC monoclonal antibody. Arch. Virol. 2005; 150 (4): 805–814. DOI: 10.1007/s00705-004-0455-z.

25. Chung W. B., Sorensen K. J., Liao P. C., Yang P. C., Jong M. H. Differentiation of foot-and-mouth disease virus-infected from vaccinated pigs by enzyme-linked immunosorbent assay using nonstructural protein 3AB as the antigen and application to an eradication program. J. Clin. Microbiol. 2002; 40 (8): 2843–2848. DOI: 10.1128/JCM.40.8.2843-2848.2002.

26. Kweon C. H., Ko Y. J., Kim W. I., Lee S. Y., Nah J. J., Lee K. N., et al. Development of a foot-and-mouth disease NSP ELISA and its comparison with differential diagnostic methods. Vaccine. 2003; 21 (13–14): 1409–1414. DOI: 10.1016/s0264-410x(02)00684-9.

27. Meyer R. F., Babcock G. D., Newman J. F., Burrage T. G., Toohey K., Lubroth J., Brown F. Baculovirus expressed 2C of foot-and-mouth disease virus hasthe potential for differentiating convalescent from vaccinated animals. J. Virol. Methods. 1997; 65 (1): 33–43. DOI: 10.1016/s0166-0934(96)02165-9.

28. BiswalJ. K., Jena S., Mohapatra J. K., Bisht P., Pattnaik B. Detection of antibodies specific for foot-and-mouth disease virus infection using indirect ELISA based on recombinant nonstructural protein 2B. Arch. Virol. 2014; 159 (7): 1641–1650. DOI: 10.1007/s00705-013-1973-3.

29. Biswal J. K., Ranjan R., Pattnaik B. Diagnostic application of recombinant non-structural protein 3A to detect antibodies induced by foot-and-mouth disease virus infection. Biologicals. 2016; 44 (3): 157–162. DOI: 10.1016/j.biologicals.2016.02.004.

30. Mahajan S., Mohapatra J. K., Pandey L. K., Sharma G. K., Pattnaik B. Truncated recombinant non-structural protein 2C-based indirect ELISA for FMD sero-surveillance. J. Virol. Methods. 2013; 193 (2): 405–414. DOI: 10.1016/j.jviromet.2013.07.003.

31. Mohapatra A. K., Mohapatra J. K., Pandey L. K., Sanyal A., Pattnaik B. Diagnostic potential of recombinant nonstructural protein 3B to detect antibodies induced by foot-and-mouth disease virus infection in bovines. Arch. Virol. 2014; 159 (9): 2359–2369. DOI: 10.1007/s00705-014-2089-0.

32. He C., Wang H., Wei H., Yan Y., Zhao T., Hu X., et al. A recombinant truncated FMDV 3AB protein used to better distinguish between infected and vaccinated cattle. Vaccine. 2010; 28 (19): 3435–3439. DOI: 10.1016/j. vaccine.2010.02.072.

33. Bergmann I. E., Malirat V., Neitzert E., Beck E., Panizzutti N., Sánchez C., Falczuk A. Improvement of a serodiagnostic strategy for foot-andmouth disease virus surveillance in cattle under systematic vaccination: a combined system of an indirect ELISA-3ABC with an enzyme-linked immunoelectrotransfer blot assay. Arch. Virol. 2000; 145 (3): 473–489. DOI: 10.1007/s007050050040.

34. Sun T., Lu P., Wang X. Localization of infection-related epitopes on the non-structural protein 3ABC of foot-and-mouth disease virus and the application of tandem epitopes. J. Virol. Methods. 2004; 119 (2): 79–86. DOI: 10.1016/j.jviromet.2004.02.016.

35. Lu Z., CaoY., Guo J., Qi S., Li D., Zhang Q., et al. Development and validation of a 3ABC indirect ELISA for differentiation of foot-and-mouth disease virusinfected from vaccinated animals. Vet. Microbiol. 2007; 125 (1–2): 157–169. DOI: 10.1016/j.vetmic.2007.05.017.

36. Zia M. A., Dobson S. J., Rowlands D. J., Stonehouse N. J., Shah M. S., Habib M. Development of an ELISA to distinguish between foot-andmouth disease virus infected and vaccinated animals utilising the viral non-structural protein 3ABC. J. Med. Microbiol. 2022; 71 (4). DOI: 10.1099/ jmm.0.001516.

37. Brocchi E., De Diego M. I., Berlinzani A., Gamba D., De Simone F. Diagnostic potential of Mab-based ELISAs for antibodies to non-structural proteins of foot-and-mouth disease virus to differentiate infection from vaccination. Vet. Q. 1998; 20 (Suppl. 2): S20–24. PMID: 9652058.

38. Sørensen K. J., Madsen K. G., Madsen E. S., Salt J. S., Nqindi J., Mackay D. K. Differentiation of infection from vaccination in foot-and-mouth disease by the detection of antibodies to the non-structural proteins 3D, 3AB and 3ABC in ELISA using antigens expressed in baculovirus. Arch. Virol. 1998; 143 (8): 1461–1476. DOI: 10.1007/s007050050390.

39. Hosamani M., Basagoudanavar S. H., Tamil Selvan R. P., Das V., Ngangom P., Sreenivasa B. P., et al. A multi-speciesindirect ELISA for detection of non-structural protein 3ABC specific antibodiesto foot-and-mouth disease virus. Arch. Virol. 2015; 160 (4): 937–944. DOI: 10.1007/s00705-015-2339-9.

40. Nanni M., Alegre M., Compaired D., Taboga O., Fondevila N. Novel purification method for recombinant 3AB1 nonstructural protein of footand-mouth disease virus for use in differentiation between infected and vaccinated animals. J. Vet. Diagn. Invest. 2005; 17 (3): 248–251. DOI: 10.117 7/104063870501700306.

41. Silberstein E., Kaplan G., Taboga O., Duffy S., Palma E. Foot-andmouth disease virus-infected but not vaccinated cattle develop antibodies against recombinant 3AB1 nonstructural protein. Arch. Virol. 1997; 142 (4): 795–805. DOI: 10.1007/s007050050119.

42. Sharma G. K., Mohapatra J. K., Mahajan S., Matura R., Subramaniam S., Pattnaik B. Comparative evaluation of non-structural protein-antibody detecting ELISAsfor foot-and-mouth disease sero-surveillance under intensive vaccination. J. Virol. Methods. 2014; 207: 22–28. DOI: 10.1016/j. jviromet.2014.06.022.

43. 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 (1–2): 14–18. DOI: 10.1016/j.vetmic.2015.04.003.

44. Bronsvoort B. M., Sørensen K. J., Anderson J., Corteyn A., Tanya V. N., Kitching R. P., Morgan K. L. Comparison of two 3ABC enzyme-linked immunosorbent assays for diagnosis of multiple-serotype foot-and-mouth disease in a cattle population in an area of endemicity. J. Clin. Microbiol. 2004; 42 (5): 2108–2114. DOI: 10.1128/JCM.42.5.2108-2114.2004.

45. Moonen P., van der Linde E., Chénard G., Dekker A. Comparable sensitivity and specificity in three commercially available ELISAsto differentiate between cattle infected with or vaccinated againstfoot-and-mouth disease virus. Vet. Microbiol. 2004; 99 (2): 93–101. DOI: 10.1016/j.vetmic.2003.12.003.

46. Lee F., Lin Y. L., Jong M. H. Comparison of ELISA for the detection of porcine serum antibodiesto non-structural proteins of foot-and-mouth disease virus. J. Virol. Methods. 2004; 116 (2): 155–159. DOI: 10.1016/j.jviromet.2003.11.004.

47. Brocchi E., Bergmann I. E., Dekker A., Paton D. J., Sammin D. J., Greiner M., et al. Comparative evaluation of six ELISAs for the detection of antibodies to the non-structural proteins of foot-and-mouth disease virus. Vaccine. 2006; 24 (47–48): 6966–6979. DOI: 10.1016/j.vaccine.2006.04.050.

48. Foot and mouth disease (infection with foot and mouth disease virus). In: WOAH. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Chapter 3.1.8. Режим доступа: https://www.woah.org/fileadmin/ Home/eng/Health_standards/tahm/3.01.08_FMD.pdf.

49. Paton D. J., Ferris N. P., Hutchings G. H., Li Y., Swabey K., Keel P., et al. Investigationsinto the cause of foot-and-mouth disease virusseropositive smallruminantsin Cyprus during 2007. Transbound. Emerg. Dis. 2009; 56 (8): 321–328. DOI: 10.1111/j.1865-1682.2009.01088.x.

50. Chitray M., Grazioli S., Willems T., Tshabalala T., De Vleeschauwer A., Esterhuysen J. J., et al. Development and validation of a foot-and-mouth disease virus SAT serotype-specific 3ABC assay to differentiate infected from vaccinated animals. J. Virol. Methods. 2018; 255: 44–51. DOI: 10.1016/j. jviromet.2018.02.006.

51. WOAH. Terrestrial Animal Health Code. Режим доступа: https:// www.woah.org/en/what-we-do/standards/codes-and-manuals/terrestrial-code-online-access.

52. Armstrong R. M., Cox S. J., Aggarwal N., Mackay D. J., Davies P. R., Hamblin P. A., et al. Detection of antibody to the foot-and-mouth disease virus (FMDV) non-structural polyprotein 3ABC in sheep by ELISA. J. Virol. Methods. 2005; 125 (2): 153–163. DOI: 10.1016/j.jviromet.2005.01.012.

53. Robiolo B., Seki C., Fondevilla N., Grigera P., Scodeller E., Periolo O., et al. Analysis of the immune response to FMDV structural and non-structural proteinsin cattle in Argentina by the combined use of liquid phase and 3ABC-ELISA tests. Vaccine. 2006; 24 (7): 997–1008. DOI: 10.1016/j.vaccine.2005.08.071.

54. Chen S. P., EllisT. M., Lee M. C., Cheng I. C., Yang P. C., LinY. L., et al. Comparison of sensitivity and specificity in three commercial foot-and-mouth disease virus non-structural protein ELISA kits with swine sera in Taiwan. Vet. Microbiol. 2007; 119 (2–4): 164–172. DOI: 10.1016/j.vetmic.2006.09.013.

55. Mohapatra J. K., Pandey L. K., Sanyal A., Pattnaik B. Recombinant non-structural polyprotein 3AB-based serodiagnostic strategy for FMD surveillance in bovines irrespective of vaccination. J. Virol. Methods. 2011; 177 (2): 184–192. DOI: 10.1016/j.jviromet.2011.08.006.

56. Lee F., Jong M. H., Yang D. W. Presence of antibodiesto non-structural proteins of foot-and-mouth disease virusin repeatedly vaccinated cattle. Vet. Microbiol. 2006; 115 (1–3): 14–20. DOI: 10.1016/j.vetmic.2005.12.017.

57. Tekleghiorghis T., Weerdmeester K., van Hemert-Kluitenberg F., Moormann R. J., Dekker A. Comparison of test methodologiesfor foot-andmouth disease virus serotype A vaccine matching. Clin. Vaccine. Immunol. 2014; 21 (5): 674–683. DOI: 10.1128/CVI.00034-14.

58. Liu Z. Z., Zhao F. R., Gao S. D., Shao J. J., Zhang Y. G., Chang H. Y. Development of a chemiluminescence immunoassay using recombinant non-structural epitope-based proteinsto accurately differentiate foot-andmouth disease virus-infected and vaccinated bovines. Transbound. Emerg. Dis. 2018; 65 (2): 338–344. DOI: 10.1111/tbed.12811.

59. Barnett P. V., Geale D. W., Clarke G., Davis J., Kasari T. R. A review of OIE country status recovery using vaccinate-to-live versus vaccinate-to-die foot-and-mouth disease response policiesI: benefits of higher potency vaccines and associated NSP DIVA testsystemsin post-outbreak surveillance. Transbound. Emerg. Dis. 2015; 62 (4): 367–387. DOI: 10.1111/ tbed.12166.

60. Yakovleva A. S., Kanshina A. V., Scherbakov A. V. Expression of recombinant nonstructural proteins 3A, 3B and 3AB of foot-and-mouth disease virus in E. coli. Proceedings of the Federal Centre for Animal Health. 2005; 3: 105–114. EDN: UNWYYB. (in Russ.)

61. Yakovleva A. S., Shcherbakov A. V., Kanshina A. V., Mudrak N. S., Fomina T. A. Recombinant non-structural 3A, 3B and 3AB proteins of footand-mouth disease virus: use in indirect ELISA for differentiation of vaccinated and infected cattle. Mol. Biol. 2006; 40 (1): 146–151. DOI: 10.1134/ S0026893306010195.

62. Yakovleva A. S., Kanshina A. V., Scherbakov A. V., Mudrak N. S., Fomina T. A. Development of an indirect ELISA based on E. coli expressed 3A, 3B and 3AB nonstructural proteins of FMDV to differentiate between infected and vaccinated cattle. Proceedings of the Federal Centre for Animal Health. 2005; 3: 115–126. EDN: UNWYYL. (in Russ.)

63. Yakovleva A., Kanshina A., Scherbakov A. Development of indirect ELISA for detection of antibodiesto foot-and-mouth disease virus nonstructural proteins. In: TheGlobalControl of FMD – Tool, Ideas and Ideals: Book and Abstr. Europ. Commiss. Control FMD. FAO; 2008; 80.

64. Yakovleva A. S., Kanshina A. V., Scherbakov A. V., Orlova Ye. S. Development and validation of 3AB-ELISA test-system for detection of antibodies to FMD virus nonstructural proteins in blood sera from cattle and small ruminants. Veterinary Science Today. 2015; (4): 36–42. EDN: VODNXP. (in Russ.)

65. Kanshina A. V., Yakovleva A. S., Orlova Y. S., Scherbakov A. V. Seromonitoring yashchura = Seromonitoring for foot-and-mouth disease. Molekulyarnayadiagnostika: sborniknauchnykhtrudovXYubileinoimezhdunarodnoi nauchno-prakticheskoi konferentsii (Moskva, 9–11 noyabrya 2021 g.) = Molecular diagnosis: Proceedings of the X Anniversary International Scientific and Practical Conference (Moscow, 9–11 2021). Tambov: OOO firma “Yulis”; 2021; 2: 349–350. EDN: FEDYZQ.