Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1994 Nov;68(11):7092–7098. doi: 10.1128/jvi.68.11.7092-7098.1994

Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies and protective immunity to multiple serotypes of FMDV.

E Rieder 1, B Baxt 1, J Lubroth 1, P W Mason 1
PMCID: PMC237147  PMID: 7523697

Abstract

The G-H loop of VP1 (residues 132 to 159) of foot-and-mouth disease virus (FMDV) is a prominent feature on the virion surface and has an important role in vaccine efficacy, generation of antigenic variants, and cell binding. Using an infectious cDNA of FMDV, we have constructed serotype A viruses in which the G-H loop has been substituted with the homologous sequences from serotype O or C. These chimeric viruses replicated to high titer and displayed plaque morphologies similar to those of wild-type viruses, demonstrating that the functions provided by the loop can be readily exchanged between serotypes. Monoclonal antibody analyses showed that epitopes contained within the loop were transferred to the chimeras and that epitopes encoded by the type A backbone were maintained. Chemically inactivated vaccines prepared from chimeric viruses induced antibodies in guinea pigs that neutralized both type A and either type O or type C viruses. Swine inoculated with the A/C chimera vaccine also produced cross-reactive antibodies, were protected from challenge with the type A virus, and partially protected against challenge with type C. These studies emphasize the importance of epitopes outside of the G-H loop in protective immunity in swine, which is a natural host of FMDV.

Full text

PDF
7092

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature. 1989 Feb 23;337(6209):709–716. doi: 10.1038/337709a0. [DOI] [PubMed] [Google Scholar]
  2. Bachrach H. L. Foot-and-mouth disease. Annu Rev Microbiol. 1968;22:201–244. doi: 10.1146/annurev.mi.22.100168.001221. [DOI] [PubMed] [Google Scholar]
  3. Bahnemann H. G. Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production. Arch Virol. 1975;47(1):47–56. doi: 10.1007/BF01315592. [DOI] [PubMed] [Google Scholar]
  4. Barnett P. V., Ouldridge E. J., Rowlands D. J., Brown F., Parry N. R. Neutralizing epitopes of type O foot-and-mouth disease virus. I. Identification and characterization of three functionally independent, conformational sites. J Gen Virol. 1989 Jun;70(Pt 6):1483–1491. doi: 10.1099/0022-1317-70-6-1483. [DOI] [PubMed] [Google Scholar]
  5. Baxt B., Becker Y. The effect of peptides containing the arginine-glycine-aspartic acid sequence on the adsorption of foot-and-mouth disease virus to tissue culture cells. Virus Genes. 1990 Jun;4(1):73–83. doi: 10.1007/BF00308567. [DOI] [PubMed] [Google Scholar]
  6. Baxt B., Morgan D. O., Robertson B. H., Timpone C. A. Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment. J Virol. 1984 Aug;51(2):298–305. doi: 10.1128/jvi.51.2.298-305.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Baxt B., Vakharia V., Moore D. M., Franke A. J., Morgan D. O. Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus. J Virol. 1989 May;63(5):2143–2151. doi: 10.1128/jvi.63.5.2143-2151.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bittle J. L., Houghten R. A., Alexander H., Shinnick T. M., Sutcliffe J. G., Lerner R. A., Rowlands D. J., Brown F. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature. 1982 Jul 1;298(5869):30–33. doi: 10.1038/298030a0. [DOI] [PubMed] [Google Scholar]
  9. Brown F. Foot-and-mouth disease--one of the remaining great plagues. Proc R Soc Lond B Biol Sci. 1986 Dec 22;229(1256):215–226. doi: 10.1098/rspb.1986.0083. [DOI] [PubMed] [Google Scholar]
  10. Cowan K. M., Graves J. H. A third antigenic component associated with foot-and-mouth disease infection. Virology. 1966 Nov;30(3):528–540. doi: 10.1016/0042-6822(66)90128-0. [DOI] [PubMed] [Google Scholar]
  11. Crowther J. R., Farias S., Carpenter W. C., Samuel A. R. 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 Aug;74(Pt 8):1547–1553. doi: 10.1099/0022-1317-74-8-1547. [DOI] [PubMed] [Google Scholar]
  12. DiMarchi R., Brooke G., Gale C., Cracknell V., Doel T., Mowat N. Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science. 1986 May 2;232(4750):639–641. doi: 10.1126/science.3008333. [DOI] [PubMed] [Google Scholar]
  13. Doel T. R., Gale C., Do Amaral C. M., Mulcahy G., Dimarchi R. Heterotypic protection induced by synthetic peptides corresponding to three serotypes of foot-and-mouth disease virus. J Virol. 1990 May;64(5):2260–2264. doi: 10.1128/jvi.64.5.2260-2264.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fox G., Parry N. R., Barnett P. V., McGinn B., Rowlands D. J., Brown F. The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginine-glycine-aspartic acid). J Gen Virol. 1989 Mar;70(Pt 3):625–637. doi: 10.1099/0022-1317-70-3-625. [DOI] [PubMed] [Google Scholar]
  15. Francis M. J., Hastings G. Z., Clarke B. E., Brown A. L., Beddell C. R., Rowlands D. J., Brown F. Neutralizing antibodies to all seven serotypes of foot-and-mouth disease virus elicited by synthetic peptides. Immunology. 1990 Feb;69(2):171–176. [PMC free article] [PubMed] [Google Scholar]
  16. Gebauer F., de la Torre J. C., Gomes I., Mateu M. G., Barahona H., Tiraboschi B., Bergmann I., de Mello P. A., Domingo E. Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle. J Virol. 1988 Jun;62(6):2041–2049. doi: 10.1128/jvi.62.6.2041-2049.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Higuchi R., Krummel B., Saiki R. K. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 1988 Aug 11;16(15):7351–7367. doi: 10.1093/nar/16.15.7351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kitson J. D., Burke K. L., Pullen L. A., Belsham G. J., Almond J. W. Chimeric polioviruses that include sequences derived from two independent antigenic sites of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies against FMDV in guinea pigs. J Virol. 1991 Jun;65(6):3068–3075. doi: 10.1128/jvi.65.6.3068-3075.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kitson J. D., McCahon D., Belsham G. J. 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 Nov;179(1):26–34. doi: 10.1016/0042-6822(90)90269-w. [DOI] [PubMed] [Google Scholar]
  20. Krebs O., Ahl R., Straub O. C., Marquardt O. Amino acid changes outside the G-H loop of capsid protein VP1 of type O foot-and-mouth disease virus confer resistance to neutralization by antipeptide G-H serum. Vaccine. 1993;11(3):359–362. doi: 10.1016/0264-410x(93)90199-8. [DOI] [PubMed] [Google Scholar]
  21. Lea S., Hernández J., Blakemore W., Brocchi E., Curry S., Domingo E., Fry E., Abu-Ghazaleh R., King A., Newman J. The structure and antigenicity of a type C foot-and-mouth disease virus. Structure. 1994 Feb 15;2(2):123–139. doi: 10.1016/s0969-2126(00)00014-9. [DOI] [PubMed] [Google Scholar]
  22. Logan D., Abu-Ghazaleh R., Blakemore W., Curry S., Jackson T., King A., Lea S., Lewis R., Newman J., Parry N. Structure of a major immunogenic site on foot-and-mouth disease virus. Nature. 1993 Apr 8;362(6420):566–568. doi: 10.1038/362566a0. [DOI] [PubMed] [Google Scholar]
  23. Makoff A. J., Paynter C. A., Rowlands D. J., Boothroyd J. C. Comparison of the amino acid sequence of the major immunogen from three serotypes of foot and mouth disease virus. Nucleic Acids Res. 1982 Dec 20;10(24):8285–8295. doi: 10.1093/nar/10.24.8285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Martin A., Wychowski C., Couderc T., Crainic R., Hogle J., Girard M. Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice. EMBO J. 1988 Sep;7(9):2839–2847. doi: 10.1002/j.1460-2075.1988.tb03140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mason P. W., Rieder E., Baxt B. RGD sequence of foot-and-mouth disease virus is essential for infecting cells via the natural receptor but can be bypassed by an antibody-dependent enhancement pathway. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1932–1936. doi: 10.1073/pnas.91.5.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mateu M. G., Da Silva J. L., Rocha E., De Brum D. L., Alonso A., Enjuanes L., Domingo E., Barahona H. Extensive antigenic heterogeneity of foot-and-mouth disease virus of serotype C. Virology. 1988 Nov;167(1):113–124. doi: 10.1016/0042-6822(88)90060-8. [DOI] [PubMed] [Google Scholar]
  27. Mateu M. G., Hernández J., Martínez M. A., Feigelstock D., Lea S., Pérez J. J., Giralt E., Stuart D., Palma E. L., Domingo E. Antigenic heterogeneity of a foot-and-mouth disease virus serotype in the field is mediated by very limited sequence variation at several antigenic sites. J Virol. 1994 Mar;68(3):1407–1417. doi: 10.1128/jvi.68.3.1407-1417.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mateu M. G., Martínez M. A., Capucci L., Andreu D., Giralt E., Sobrino F., Brocchi E., Domingo E. A single amino acid substitution affects multiple overlapping epitopes in the major antigenic site of foot-and-mouth disease virus of serotype C. J Gen Virol. 1990 Mar;71(Pt 3):629–637. doi: 10.1099/0022-1317-71-3-629. [DOI] [PubMed] [Google Scholar]
  29. Mateu M. G., Martínez M. A., Rocha E., Andreu D., Parejo J., Giralt E., Sobrino F., Domingo E. Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5883–5887. doi: 10.1073/pnas.86.15.5883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Minor P. D., Ferguson M., Katrak K., Wood D., John A., Howlett J., Dunn G., Burke K., Almond J. W. Antigenic structure of chimeras of type 1 and type 3 poliovirus involving antigenic site 1. J Gen Virol. 1990 Nov;71(Pt 11):2543–2551. doi: 10.1099/0022-1317-71-11-2543. [DOI] [PubMed] [Google Scholar]
  31. Murdin A. D., Wimmer E. Construction of a poliovirus type 1/type 2 antigenic hybrid by manipulation of neutralization antigenic site II. J Virol. 1989 Dec;63(12):5251–5257. doi: 10.1128/jvi.63.12.5251-5257.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Murray M. G., Kuhn R. J., Arita M., Kawamura N., Nomoto A., Wimmer E. Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys. Proc Natl Acad Sci U S A. 1988 May;85(9):3203–3207. doi: 10.1073/pnas.85.9.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Parry N., Fox G., Rowlands D., Brown F., Fry E., Acharya R., Logan D., Stuart D. Structural and serological evidence for a novel mechanism of antigenic variation in foot-and-mouth disease virus. Nature. 1990 Oct 11;347(6293):569–572. doi: 10.1038/347569a0. [DOI] [PubMed] [Google Scholar]
  34. Pfaff E., Thiel H. J., Beck E., Strohmaier K., Schaller H. Analysis of neutralizing epitopes on foot-and-mouth disease virus. J Virol. 1988 Jun;62(6):2033–2040. doi: 10.1128/jvi.62.6.2033-2040.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Piccone M. E., Kaplan G., Giavedoni L., Domingo E., Palma E. L. VP1 of serotype C foot-and-mouth disease viruses: long-term conservation of sequences. J Virol. 1988 Apr;62(4):1469–1473. doi: 10.1128/jvi.62.4.1469-1473.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rieder E., Bunch T., Brown F., Mason P. W. Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice. J Virol. 1993 Sep;67(9):5139–5145. doi: 10.1128/jvi.67.9.5139-5145.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Robertson B. H., Grubman M. J., Weddell G. N., Moore D. M., Welsh J. D., Fischer T., Dowbenko D. J., Yansura D. G., Small B., Kleid D. G. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J Virol. 1985 Jun;54(3):651–660. doi: 10.1128/jvi.54.3.651-660.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rueckert R. R., Wimmer E. Systematic nomenclature of picornavirus proteins. J Virol. 1984 Jun;50(3):957–959. doi: 10.1128/jvi.50.3.957-959.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Salt J. S. The carrier state in foot and mouth disease--an immunological review. Br Vet J. 1993 May-Jun;149(3):207–223. doi: 10.1016/S0007-1935(05)80168-X. [DOI] [PubMed] [Google Scholar]
  40. Stave J. W., Card J. L., Morgan D. O., Vakharia V. N. Neutralization sites of type O1 foot-and-mouth disease virus defined by monoclonal antibodies and neutralization-escape virus variants. Virology. 1988 Jan;162(1):21–29. doi: 10.1016/0042-6822(88)90390-x. [DOI] [PubMed] [Google Scholar]
  41. Thomas A. A., Woortmeijer R. J., Puijk W., Barteling S. J. Antigenic sites on foot-and-mouth disease virus type A10. J Virol. 1988 Aug;62(8):2782–2789. doi: 10.1128/jvi.62.8.2782-2789.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Xie Q. C., McCahon D., Crowther J. R., Belsham G. J., McCullough K. C. Neutralization of foot-and-mouth disease virus can be mediated through any of at least three separate antigenic sites. J Gen Virol. 1987 Jun;68(Pt 6):1637–1647. doi: 10.1099/0022-1317-68-6-1637. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES