Skip to main content

Advertisement

SpringerLink
Log in

The rescue and selection of thermally stable type O vaccine candidate strains of foot-and-mouth disease virus

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Inactivated foot-and-mouth disease virus (FMDV) vaccines have been used widely to control foot-and-mouth disease (FMD). However, the virions (146S) of this virus are easily dissociated into pentamer subunits (12S), which limits the immune protective efficacy of inactivated vaccines when the temperature is higher than 30 °C. A cold-chain system can maintain the quality of the vaccines, but such systems are usually not reliable in limited-resource settings. Thus, it is imperative to improve the thermostability of vaccine strains to guarantee the quality of the vaccines. In this study, four recombinant FMDV strains containing single or multiple amino acid substitutions in the structural proteins were rescued using a previously constructed FMDV type O full-length infectious clone (pO/DY-VP1). We found that single or multiple amino acid substitutions in the structural proteins affected viral replication to different degrees. Furthermore, the heat and acid stability of the recombinant viruses was significantly increased when compared with the parental virus. Three thermally stable recombinant viruses (rHN/DY-VP1Y2098F, rHN/DY-VP1V2090A-S2093H, and rHN/DY-VP1V2090A-S2093H-Y2098F) were prepared as inactivated vaccines to immunize pigs. Blood samples were collected every week to prepare sera, and a virus neutralization test showed that the substitutions S2093H and Y2098F, separately or in combination, did not affect the immunogenicity of the virus, but the Y2098F mutation increased the thermostability significantly (p < 0.05). Therefore, the rHN/DY-VP1Y2098F mutant should be considered for use in future vaccines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Alexandersen S, Zhang Z, Donaldson AI, Garland AJ (2003) The pathogenesis and diagnosis of foot-and-mouth disease. J Comp Pathol 129(1):1–36. https://doi.org/10.1016/s0021-9975(03)00041-0

    Article  CAS  PubMed  Google Scholar 

  2. Brown F (2003) The history of research in foot-and-mouth disease. Virus Res 91(1):3–7. https://doi.org/10.1016/s0168-1702(02)00268-x

    Article  CAS  PubMed  Google Scholar 

  3. Sobrino F, Saiz M, Jimenez-Clavero MA, Nunez JI, Rosas MF, Baranowski E, Ley V (2001) Foot-and-mouth disease virus: a long known virus, but a current threat. Vet Res 32(1):1–30. https://doi.org/10.1051/vetres:2001106

    Article  CAS  PubMed  Google Scholar 

  4. Doel TR, Baccarini PJ (1981) Thermal stability of foot-and-mouth disease virus. Adv Virol 70(1):21–32. https://doi.org/10.1007/BF01320790

    Article  CAS  Google Scholar 

  5. Doel TR, Chong WK (1982) Comparative immunogenicity of 146S, 75S and 12S particles of foot-and-mouth disease virus. Arch Virol 73(2):185–191. https://doi.org/10.1007/BF01314726

    Article  CAS  PubMed  Google Scholar 

  6. Curry S, Abrams CC, Fry E, Crowther JC, Belsham GJ, Stuart DI, King AM (1995) Viral RNA modulates the acid sensitivity of foot-and-mouth disease virus capsids. J Virol 69(1):430–438. https://doi.org/10.1128/JVI.69.1.430-438.1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Newman JF, Rowlands DJ, Brown F (1973) A physico-chemical sub-grouping of the mammalian picornaviruses. J Gen Virol 18(2):171–180. https://doi.org/10.1099/0022-1317-18-2-171

    Article  CAS  PubMed  Google Scholar 

  8. Vázquez-Calvo A, Caridi F, Sobrino F, Martín-Acebes MA (2014) An increase in acid resistance of foot-and-mouth disease virus capsid is mediated by a tyrosine replacement of the VP2 histidine previously associated with VP0 cleavage. J Virol 88(5):3039–3042. https://doi.org/10.1128/JVI.03222-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kitching P, Hammond J, Jeggo M, Charleston B, Paton D, Rodriguez L, Heckert R (2007) Global FMD control–is it an option? Vaccine 25(30):5660–5664. https://doi.org/10.1016/j.vaccine.2006.10.052

    Article  PubMed  Google Scholar 

  10. Hunter P (1996) The performance of southern African territories serotypes of foot and mouth disease antigen in oil-adjuvanted vaccines. Rev Sci Tech 15 (3):913-922. https://doi.org/10.20506/rst.15.3.954

  11. Parida S (2009) Vaccination against foot-and-mouth disease virus: strategies and effectiveness. Expert Rev Vaccines 8(3):347–365. https://doi.org/10.1586/14760584.8.3.347

    Article  CAS  PubMed  Google Scholar 

  12. Cox SJ, Aggarwal N, Statham RJ, Barnett PV (2003) Longevity of antibody and cytokine responses following vaccination with high potency emergency FMD vaccines. Vaccine 21(13–14):1336–1347. https://doi.org/10.1016/s0264-410x(02)00691-6

    Article  CAS  PubMed  Google Scholar 

  13. Doel TR (2003) FMD vaccines. Virus Res 91(1):81–99. https://doi.org/10.1016/s0168-1702(02)00261-7

    Article  CAS  PubMed  Google Scholar 

  14. Hall MD, Knowles NJ, Wadsworth J, Rambaut A, Woolhouse ME (2013) Reconstructing geographical movements and host species transitions of foot-and-mouth disease virus serotype SAT 2. mBio 4 (5):e00591-00513. https://doi.org/10.1128/mBio.00591-13

  15. Schlehuber LD, McFadyen IJ, Shu Y, Carignan J, Duprex WP, Forsyth WR, Ho JH, Kitsos CM, Lee GY, Levinson DA, Lucier SC, Moore CB, Nguyen NT, Ramos J, Weinstock BA, Zhang J, Monagle JA, Gardner CR, Alvarez JC (2011) Towards ambient temperature-stable vaccines: the identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay. Vaccine 29(31):5031–5039. https://doi.org/10.1016/j.vaccine.2011.04.079

    Article  CAS  PubMed  Google Scholar 

  16. Chen X, Fernando GJ, Crichton ML, Flaim C, Yukiko SR, Fairmaid EJ, Corbett HJ, Primiero CA, Ansaldo AB, Frazer IH, Brown LE, Kendall MA (2011) Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization. J Control Release 152(3):349–355. https://doi.org/10.1016/j.jconrel.2011.02.026

    Article  CAS  PubMed  Google Scholar 

  17. Das P (2004) Revolutionary vaccine technology breaks the cold chain. Lancet Infect Dis 4(12):719. https://doi.org/10.1016/s1473-3099(04)01222-8

    Article  PubMed  Google Scholar 

  18. Wang G, Cao RY, Chen R, Mo L, Han JF, Wang X, Xu X, Jiang T, Deng YQ, Lyu K, Zhu SY, Qin ED, Tang R, Qin CF (2013) Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions. Proc Natl Acad Sci USA 110(19):7619–7624. https://doi.org/10.1073/pnas.1300233110

    Article  PubMed  PubMed Central  Google Scholar 

  19. Mateo R, Luna E, Rincon V, Mateu MG (2008) Engineering viable foot-and-mouth disease viruses with increased thermostability as a step in the development of improved vaccines. J Virol 82(24):12232–12240. https://doi.org/10.1128/JVI.01553-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kotecha A, Seago J, Scott K, Burman A, Loureiro S, Ren J, Porta C, Ginn HM, Jackson T, Perez-Martin E, Siebert CA, Paul G, Huiskonen JT, Jones IM, Esnouf RM, Fry EE, Maree FF, Charleston B, Stuart DI (2015) Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design. Nat Struct Mol Biol 22(10):788–794. https://doi.org/10.1038/nsmb.3096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Scott KA, Kotecha A, Seago J, Ren J, Fry EE, Stuart DI, Charleston B, Maree FF (2017) SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability. J Virol 91(10):e02312–e02316. https://doi.org/10.1128/JVI.02312-16

    Article  PubMed  PubMed Central  Google Scholar 

  22. Cao WJ, Li PH, Bai XW, Lu ZJ, Sun P, Liu ZX (2010) Rescue and Identification of Virus Activity of Foot-and-Mouth Disease Virus Strain O/HN/93 from Full-length cDNA Clone. ACTA Agric Boreal Sin 25(3):32–37. https://doi.org/10.7668/hbnxb.2010.03.008

    Article  Google Scholar 

  23. Sambrook J, Fritsch EF, Maniatis T (1982) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, New York

    Google Scholar 

  24. Rieder E, Bunch T, Brown F, Mason PW (1993) Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice. J Virol 67(9):5139–5145. https://doi.org/10.1128/JVI.67.9.5139-5145.1993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pacheco JM, Henry TM, O’Donnell VK, Gregory JB, Mason PW (2003) Role of nonstructural proteins 3A and 3B in host range and pathogenicity of foot-and-mouth diseasevirus. J Virol 77(24):13017–13027. https://doi.org/10.1128/jvi.77.24.13017-13027.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Knipe T, Rieder E, Baxt B, Ward G, Mason PW (1997) Characterization of synthetic foot-and-mouth disease virus provirions separates acid-mediated disassembly from infectivity. J Virol 71(4):2851–2856. https://doi.org/10.1128/JVI.71.4.2851-2856.1997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mateo R, Luna E, Mateu MG (2007) Thermostable variants are not generally represented in foot-and-mouth disease virus quasispecies. J Gen Virol 88(Pt 3):859–864. https://doi.org/10.1099/vir.0.82521-0

    Article  CAS  PubMed  Google Scholar 

  28. Mateo R, Mateu MG (2007) Deterministic, compensatory mutational events in the capsid of foot-and-mouth disease virus in response to the introduction of mutations found in viruses from persistent infections. J Virol 81(4):1879–1887. https://doi.org/10.1128/JVI.01899-06

    Article  CAS  PubMed  Google Scholar 

  29. Mateo R, Diaz A, Baranowski E, Mateu MG (2003) Complete alanine scanning of intersubunit interfaces in a foot-and-mouth disease virus capsid reveals critical contributions of many side chains to particle stability and viral function. J Biol Chem 278(42):41019–41027. https://doi.org/10.1074/jbc.M304990200

    Article  CAS  PubMed  Google Scholar 

  30. Fowler VL, Bashiruddin JB, Maree FF, Mutowembwa P, Bankowski B, Gibson D, Cox S, Knowles N, Barnett PV (2011) Foot-and-mouth disease marker vaccine: cattle protection with a partial VP1 G-H loop deleted virus antigen. Vaccine 29(46):8405–8411. https://doi.org/10.1016/j.vaccine.2011.08.035

    Article  CAS  PubMed  Google Scholar 

  31. OIE (2012) FMD. Manual of Standard for Diagnostic Test and Vaccine. OIE, Paris, pp 77–92

    Google Scholar 

  32. Shao J-J, Wong CK, Lin T, Lee SK, Cong G-Z, Sin FWY, Du J-Z, Gao S-D, Liu X-T, Cai X-P, Xie Y, Chang H-Y, Liu J-X (2011) Promising multiple-epitope recombinant vaccine against foot-and-mouth disease virus type O in swine. Clin Vaccine Immunol 18(1):143–149. https://doi.org/10.1128/CVI.00236-10

    Article  CAS  PubMed  Google Scholar 

  33. Barnett PV, Statham RJ, Vosloo W, Haydon DT (2003) Foot-and-mouth disease vaccine potency testing: determination and statistical validation of a model using a serological approach. Vaccine 21(23):3240–3248. https://doi.org/10.1016/s0264-410x(03)00219-6

    Article  CAS  PubMed  Google Scholar 

  34. Bolwell C, Parry NR, Rowlands DJ (1992) Comparison between in vitro neutralization titres and in vivo protection against homologous and heterologous challenge induced by vaccines prepared from two serologically distinct variants of foot-and-mouth disease virus, serotype A22. J Gen Virol 73(3):727–731. https://doi.org/10.1099/0022-1317-73-3-727

    Article  PubMed  Google Scholar 

  35. Brehm KE, Ferris NP, Lenk M, Riebe R, Haas B (2009) Highly sensitive fetal goat tongue cell line for detection and isolation of foot-and-mouth disease virus. J Clin Microbiol 47(10):3156–3160. https://doi.org/10.1128/JCM.00510-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Luongo C, Winter CC, Collins PL, Buchholz UJ (2012) Increased genetic and phenotypic stability of a promising live-attenuated respiratory syncytial virus vaccine candidate by reverse genetics. J Virol 86(19):10792–10804. https://doi.org/10.1128/JVI.01227-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Schulze P, Olechnowitz AF (1975) Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. III. Morphogenesis in cytoplasm. Arch Exp Veterinarmed 29(3):441–457

    CAS  PubMed  Google Scholar 

  38. Loladze VV, Ibarra-Molero B, Sanchez-Ruiz JM, Makhatadze GI (1999) Engineering a thermostable protein via optimization of charge-charge interactions on the protein surface. Biochemistry 38(50):16419–16423. https://doi.org/10.1021/bi992271w

    Article  CAS  PubMed  Google Scholar 

  39. Rincón V, Rodríguez-Huete A, López-Argüello S, Ibarra-Molero B, Sanchez-Ruiz Jose M, Harmsen Michiel M, Mateu Mauricio G (2014) Identification of the structural basis of thermal lability of a virus provides a rationale for improved vaccines. Structure 22(11):1560–1570. https://doi.org/10.1016/j.str.2014.08.019

    Article  CAS  PubMed  Google Scholar 

  40. O’Donnell V, LaRocco M, Duque H, Baxt B (2005) Analysis of foot-and-mouth disease virus internalization events in cultured cells. J Virol 79(13):8506–8518. https://doi.org/10.1128/JVI.79.13.8506-8518.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ganji VK, Biswal JK, Lalzampuia H, Basagoudanavar SH, Saravanan P, Tamil Selvan RP, Umapathi V, Reddy GR, Sanyal A, Dechamma HJ (2018) Mutation in the VP2 gene of P1–2A capsid protein increases the thermostability of virus-like particles of foot-and-mouth disease virus serotype O. Appl Microbiol Biotechnol 102(20):8883–8893. https://doi.org/10.1007/s00253-018-9278-9

    Article  CAS  PubMed  Google Scholar 

  42. Yuan H, Li P, Bao H, Sun P, Bai X, Bai Q, Li N, Ma X, Cao Y, Fu Y, Li K, Zhang J, Li D, Chen Y, Zhang J, Lu Z, Liu Z (2020) Engineering viable foot-and-mouth disease viruses with increased acid stability facilitate the development of improved vaccines. Appl Microbiol Biotechnol 104(4):1683–1694. https://doi.org/10.1007/s00253-019-10280-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by National Key Research and Development Programs (2017YFD0500902) and the Gansu Youth Science and Technology Fund Project (1606RJYA256).

Author information

Author notes

    Authors and Affiliations

    1. State Key Laboratory of Veterinary Etiologic Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China

      Ya Gao, Pinghua Li, Xueqing Ma, Xingwen Bai, Pu Sun, Ping Du, Hong Yuan, Yimei Cao, Kun Li, Yuanfang Fu, Jing Zhang, Huifang Bao, Yingli Chen, Zhiyong Li, Zengjun Lu, Zaixin Liu & Dong Li

    Authors
    1. Ya Gao
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Pinghua Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Xueqing Ma
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Xingwen Bai
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Pu Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Ping Du
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Hong Yuan
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Yimei Cao
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Kun Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Yuanfang Fu
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Jing Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Huifang Bao
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Yingli Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Zhiyong Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. Zengjun Lu
      View author publications

      You can also search for this author in PubMed Google Scholar

    16. Zaixin Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    17. Dong Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Zengjun Lu, Zaixin Liu or Dong Li.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Additional information

    Handling Editor: Sheela Ramamoorthy.

    Publisher's Note

    Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

    Ya Gao and Pinghua Li have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Gao, Y., Li, P., Ma, X. et al. The rescue and selection of thermally stable type O vaccine candidate strains of foot-and-mouth disease virus. Arch Virol 166, 2131–2140 (2021). https://doi.org/10.1007/s00705-021-05100-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00705-021-05100-3

    Search

    Navigation