Foot-and-Mouth Disease and Its Antigens

  • Howard L. Bachrach
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 185)


Many factors combine to make foot-and-mouth disease (FMD) one of the most damaging and intractable disease of animals. These include its extreme contagion, wide geographic distribution, great multiplicity of both susceptible animal hosts and viral serotypes, a relatively short duration of immunity to a given serotype and a post-recovery carrier state of the virus in many animal species (e.g., cattle, sheep and goats). Nevertheless, import restrictions and other actions of the U.S. Government have kept the United States free of FMD since 1929, even during outbreaks of the disease in Mexico and Canada in the early 1950’s. Beginning in the late 1940’s, the systematic vaccination of cattle has been practiced in several areas of the world with varying degrees of success. While this procedure has succeeded in Western Europe in greatly reducing the incidence of FMD, the presence of live virus in some batches of vaccine and the escape of virus from vaccine from manufacturing facilities are now responsible for a large proportion of the outbreaks that still occur there. A vaccine is needed that has no possibility of producing the disease. During the last few years, it has been demonstrated that capsid protein VP1, isolated from type A and C virions or biosynthesized in E. coli transformed with the gene for VP1, can be used to immunize livestock against FMD. Immunization of livestock has also been achieved with a 13 kd fragment (amino acid residues 55 through 179) cleaved with CNBr from the 213 amino acid long VP1 chain of type A virions. Immunogenic sites on intact virions, 12 S subunit particles and isolated VP1 chains have been studied by a combination of methods, including: 1) assessment of the immunogenicity of VP1-specific fragments and synthetic peptides and 2) mapping monoclonal antibodies (Mabs) generated with virus, VP1 and the 13 kd fragment to virus, 12 S subunits, VP1, VP1-specific fragments and a biosynthetic 32mer. Correlation of these results with sites having variant and serotype sequence variability indicates that the 136–179 region of type Al2 VP1 possesses four putative neutralization-specific epitopes (ca. 137–143, 146–151, 152–157 and 170–175). Of three neutralization-specific epitopes on type Al2 virus, two are also present on 12 S subunits and isolated VP1 chains. Mabs to the three epitopes appear to neutralize virus by different mechanisms: by viral aggregation, by blocking the site on viral VP1 that binds to cell receptors or by interfering with a postreceptor attachment step, possibly penetration or uncoating.

Although a peptide synthesized chemically to correspond to amino acid residues 141–160 of type O1 VP1 has been shown to produce protective immunity in guinea pigs (Bittle et al., 1982), it has so far been ineffective in cattle. An epitope (residues 146–152) on type O1 virus and VP1, co-sequential with the type Al2 146–151 epitope, has been detected by the binding of antibody to 208 overlapping hexapeptides covering the entire length of VP1 (Geysen et al., 1984). Using residue replacement synthetic peptides, the epitope was shown to have an absolute requirement for leucyl residues 148 and 151. The coincidence on VP1 of this type O1 epitope and a type Al2 putative epitope strengthens the evidence that variant and serotype changes in FMD virus can both stem from a common precursor epitope sequence.


Disease Virus Capsid Protein Protective Immunity Induce Neutralize Antibody Putative Epitope 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Atassi, M. Z., and Sakata, S., 1980, Antibodies to synthetic antibody-combining sites. Antibodies against a surface simulation peptide with antibody-combining activity toward lysozyme antigenic site 3 react with lysozyme antibodies, Biochem. Biophys. Acta., 624: 573.PubMedGoogle Scholar
  2. Bachrach, H. L., 1952, The determination of the sedimentation constant of a homogeneous component having the characteristics of the foot-and-mouth disease virus, Am. J. Vet. Res., 13: 13.PubMedGoogle Scholar
  3. Bachrach, H. L., 1968, Foot-and-mouth disease, in: “Annual Review of Microbiology,” C. E. Clifton, S. Raffel and M. P. Starr, eds., v 22, p. 201, Annual Reviews Inc., Palo Alto.Google Scholar
  4. Bachrach, H. L., 1977, Foot-and-mouth disease virus: Properties, molecular biology and immunogenicity, in: “Beltsville Symposium in Agricultural Research, I. Virology in Agriculture,” J. A. Romberger, ed., pp. 3–32, Allenheld Osmun and Co., Montclair.Google Scholar
  5. Bachrach, H. L., 1978, Foot-and-mouth disease: Worldwide impact and control measures, in: “Viruses and Environment,” K. Maramorosch and E. Kurstak, eds., p. 229, Academic Press, NY.Google Scholar
  6. Bachrach, H. L., Callis, J. J., Hess, W. R., and Patty, R. E., 1957, A plaque assay for foot-and-mouth disease virus and kinetics of virus reproduction, Vir~olo y, 4: 224.Google Scholar
  7. Bachrach, H. L., and Breese, S. S. Jr., 1958, Purification and electron microscopy of foot-and-mouth disease virus, Proc. Soc. Exp. Biol. Med., 97: 659.PubMedGoogle Scholar
  8. Bachrach, H. L., Hess, W. R., and Callis, J. J., 1955, Foot-and-mouth disease virus: Its growth and cytopathogenicity in tissue culture, Science 122: 1269.PubMedCrossRefGoogle Scholar
  9. Bachrach, H. L., and McKercher, P. D., 1972, Immunology of FMD in swine: Experimental inactivated-virus vaccine, J. Am. Vet. Med. Assoc, 160: 521.PubMedGoogle Scholar
  10. Bachrach, H. L., Moore, D. M., McKercher, P. D., and Polatnick, J., 1975, Immune and antibody responses to an isolated capsid protein of foot-and-mouth disease virus, J. Immunol., 115: 1636.Google Scholar
  11. Bachrach, H. L., Moore, D. M., McKercher, P. D., and Polatnick, J., 1978, An experimental protein vaccine for foot-and-mouth disease, in: “Perspectives in Virology X,” M. Pollard, ed., pp. 147, Raven Press, NY.Google Scholar
  12. Bachrach, H. L., Morgan, D. 0., McKercher, P. D., Moore, D. M., and Robertson, B. H., 1982, Immunogenicity and structure of fragments derived from foot-and-mouth disease virus capsid protein VP3 and of virions having intact and cleaved VP3, Vet. Microbiol., 7: 85.PubMedCrossRefGoogle Scholar
  13. Bachrach, H. L., Morgan, D. 0., and Moore, D. M., 1979, Foot-and-mouth disease virus immunogenic capsid protein VPT: N terminal sequences and immunogenic peptides obtained by CNBr and tryptic cleavages, Intervirology 12: 65.Google Scholar
  14. Bachrach, H. L., and Schwerdt, C. E., 1954, Purification studies on Lansing poliomyelitis virus II. Analytical electron microscopic identification of the infectious particle in preparations of high specific infectivity, J. Immunol., 72: 30.PubMedGoogle Scholar
  15. Bachrach, H. L., Swaney, J. B., and Vande Woude, G. F., 1973, Isolation of the structural polypeptides of foot-and-mouth disease virus and analysis of their C-terminal sequences, Virology 52: 520.PubMedCrossRefGoogle Scholar
  16. Bachrach, H. L., Trautman, R., and Breese, S. S. Jr., 1964, Chemical and physical properties of virtually pure foot-and-mouth disease virus, Am. J. Vet. Res., 25: 333.PubMedGoogle Scholar
  17. Baxt, B., Morgan, D. 0., Robertson, B. H., and Timpone, C. A., 1984, Epitopes on foot-and-mouth disease outer capsid protein VP1 involved in neutralization and cell attachment, J. Virol., 51: 298.Google Scholar
  18. Beck, E., Feil, G., and Strohmaier, K., 1983, The molecular basis of the antigenic variation of foot-and-mouth disease virus. EMBO, J., 2: 555.Google Scholar
  19. Bernard, S., Wantyghem, J., Grosclaude, J., and Laporte, J., 1974, Chromatographic separation of purified structural proteins from foot-and-mouth disease virus, Biochem. Biophys. Res. Commun., 58: 624.PubMedCrossRefGoogle Scholar
  20. Bittle, J. L., Houghten, R. A., Alexander, H., Shinnick, T. M., Sutcliffe, J. G., Lerner, R. A., Rowlands, D. J., and Brown, F., 1982, Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence, Nature (London) 298: 30.CrossRefGoogle Scholar
  21. Carrol, A. R., Rowlands, D. J., and Clarke, B. E., 1984, The complete nucleotide sequence of the RNA coding for the primary translation product of foot-and-mouth disease virus, Nucleic Acids Res, 12: 2461.CrossRefGoogle Scholar
  22. Cartwright, B., Morrell, D. J., and Brown F., 1982, Nature of the antibody response to the foot-and-mouth disease virus particle, its 12S protein subunit and the isolated immunizing polypeptide VP1, J. Gen. Virol., 63: 375.PubMedCrossRefGoogle Scholar
  23. Forss, S., and Schaller, H., 1982, A tanden repeat gene in a picornavirus, Nucleic Acids Res, 10: 6441.PubMedCrossRefGoogle Scholar
  24. Frascastorius, H., 1546, De allis differcattis contagionis, in: “De Sympathia et Antipathia Rerum Liber Unus, De contagions et contagiosis morbis et curatione, Bk 1, Chap. 12, Venecia.Google Scholar
  25. Frenkel, H. S., 1951, Research on foot-and-mouth disease III. The cultivation of the virus on a practical scale in explantations of bovine tongue epithelium, Am. J. Vet Res., 12: 187.PubMedGoogle Scholar
  26. Geysen, H. M., Meloen, R. H., and Barteling, 1984, Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid, Proc. Natl. Acad. Sci. USA, 81: 3998.PubMedCrossRefGoogle Scholar
  27. Kitamura, N., Semler, B. L., Rothberg, P. G., Larsen, G. R., Alder, C. J., Dorner, A. J., Emini, A., Homecak, R., Lee, J. J., Vander der Werf, S., Anderson, C. W., and Wimmer, E., 1981, Primary structure, gene organization and polypeptide expression of poliovirus RNA, Nature 291: 547.PubMedCrossRefGoogle Scholar
  28. Kleid, D. G., 1983, Using genetically-engineered bacteria for vaccine production, Annals NY Acad. Sci., 413: 23.CrossRefGoogle Scholar
  29. Klump, W., Marquardt, 0., and Hofschneider, P. H., 1984, Biologically-active protease of foot-and-mouth disease virus is expressed from cloned cDNA in Escherichia coli, Proc. Natl. Acd. Sci. USA, 81: 3351.CrossRefGoogle Scholar
  30. Kurz, C., Forss, S., Kupper, H., Strohmaier, K., and Schaller, H., 1981, Nucleotide sequence and corresponding amino acid sequence of the gene for the major antigen of foot-and-mouth disease virus, Nucleic Acids Res, 9: 1919.PubMedCrossRefGoogle Scholar
  31. Laporte, J., Grosclaude, J., Wantyghem, J., Bernard, S., and Rouge, P., 1973, Neutralization en culture cellulaire du pouvair infectieux du virus de la fievze aphteuse par des serums provenant de porcs immunises a l’aide d’une proteine virale purifiee, C. R. Acad. Sci., 276: 3399.Google Scholar
  32. Loeffler, F., and Frosch, P., 1897, Summarischer bericht uber ergebnisse der untersuchungen der kommission zur erforschung der maul-und klauenseuche bei den Institute fur Infektions-krankheiten in Berlin, Centr. Bakt. Parasitenk. Infekt. Abt., I., Orig., 22: 257.Google Scholar
  33. McCullough, K. C., and Butcher, R., 1982, Monoclonal antibodies against foot-and-mouth disease 146S and 12S particles, Arch. Virol., 74: 1.PubMedCrossRefGoogle Scholar
  34. McKercher, P. D., Moore, D. M., Morgan, D. O., Robertson, B. H., Callis, J. J., Kleid, D. G., Shire, S. J., Yansura, D. G., Dowbenko, D., and Small, B., Dose response evaluation of a genetically-engineered foot-and-mouth disease virus polypeptide immunogen in cattle, Am. J. Vet. Res., in press.Google Scholar
  35. Moore, D.M., 1983, Production of a vaccine for foot-and-mouth disease through gene cloning, in: “Genetic Engineering: Applications to Agriculture,” Beltsville Symposium VII, L. D. Owens, ed., Rowman and Allanheld, Totowa.Google Scholar
  36. Moore, D., Morgan, D., Robertson, B., McKercher, P., Patzer, E., Shire S., Kleid, D. G., 1983, A highly antigenic portion of FMDV 01 VP1 elicits bovine antibodies which protect mice but not cattle from FMDV infection, in: Abstracts “Modern Approaches to Vaccines,” Cold Spring Harbor Laboratory, Cold Spring Harbor.Google Scholar
  37. Morgan, D. O., McKercher, P. D., and Bachrach, H. L., 1970, Quantitation of the antigenicity and immunogenicity of purified foot-and-mouth disease virus vaccines for swine and steers, Appl. Microbiol., 20: 770.PubMedGoogle Scholar
  38. Morgan, D. O., Moore, D. M., Robertson, B. H., Shire, S. J., Bock L. A., and Kleid, D. G., 1983, Immunization of swine with defined segments on FMDV VP1 produced by recombinant DNA procedures, Abs 211, 64th Cong. Res. Workers Animal Dis., Chicago.Google Scholar
  39. Morgan, D. O., Robertson, B. H., Moore, D. M., Timpone, C. A., and McKercher, P. D., 1984, Aphthoviruses: Control of foot-and-mouth disease with genetic engineering vaccines, in, “Control of Virus Diseases,” E. Kurstak, ed., Marcel Dekker, NY.Google Scholar
  40. Mussgay, M., 1959, Uber den mechanismus der pH-inaktivierung des virus der maul-und-klauenseuche, Monatsh. Tierheilk., 11: 185.Google Scholar
  41. Palmenberg, A. C., Kirby, E.M., Janda, M. R., Drake, N. L., Duke, G. M., Potratz, K. F., and Collett, M. S., 1984, The nucleotide and deduced amino acid sequence of the encephalomycarditis viral polyprotein coding region, Nucleic Acids Res, 12: 2969.PubMedCrossRefGoogle Scholar
  42. Pfaff, E., Mussgay, M., Bohm, H. O., Schulz, G. E., and Schaller, H., 1982, Antibodies against a preselected peptide recognize and neutralize foot-and-mouth disease virus, EMBO J, 1: 869.PubMedGoogle Scholar
  43. Robertson, B. H., Moore, D. M., Grubman, M. J., and Kleid, D. G., 1983a, Identification of an exposed region of the immunogenic capsid polypeptide VP1 on foot-and-mouth disease virus, J. Virol., 46: 311.PubMedGoogle Scholar
  44. Robertson, B. H., Morgan, D. O., Moore, D. M., Grubman, M. J., Card, J., Fischer, T., Weddell, G. N., Dowbenko, D. J., and Yansura, D. G., 1983, Identification of amino acid and nucleotide sequence of the foot-and-mouth disease virus RNA polymerase, Virology 126: 614.PubMedCrossRefGoogle Scholar
  45. Robertson, B. H., Morgan, D. O., and Moore, D. M., Location of neutralizing epitopes defined by monoclonal antibodies generated against the outer capsid polypeptide VP1 of foot-and-mouth disease virus Al2, Virus Research, in press.Google Scholar
  46. Rowlands, D. J., Clarke, B. E., Carrol, A. R., Brown, F., Nicholson, B. H., Bittle, J. L., Houghten, R. A., and Lerner, R. A., 1983, Chemical basis of antigenic variation in foot-and-mouth disease virus, Nature 306: 694.PubMedCrossRefGoogle Scholar
  47. Rueckert, R. R., and Wimmer, E., 1984, Systematic nomenclature of picornavirus proteins, J. Virol., 50: 957.PubMedGoogle Scholar
  48. Strohmaier, K., Franze, R., and Adam, K. H., 1982, Location and characterization of the antigenic portion of the FMDV immunizing protein, J. Gen. Virol., 59: 295.PubMedCrossRefGoogle Scholar
  49. Schmidt, S., 1936, Immunisierung des meerschuoinchons gegen drei verschiedene typen von maul-und-klauensechevirus vermittels eines trivalent aluminum-hydroxydadsorbates, Z. Immunitatforsch., 88: 91.Google Scholar
  50. Waldmann, O., and Kobe, K., 1938, Active immunization of cattle against FMD, Berlin. Tierarztl. Wochschr., 22: 317.Google Scholar
  51. Wild, T. F., Burroughs, J. N., and Brown F., 1969, Surface structure of foot-and-mouth disease virus, J. Gen. Virol., 4: 313.PubMedCrossRefGoogle Scholar
  52. Wilson, T., 1984, Engineering tomorrow’s vaccines, Biotechnology 2: 29.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Howard L. Bachrach
    • 1
  1. 1.Plum Island Animal Disease Center U.S. Department of AgricultureARSGreenportUSA

Personalised recommendations