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J Virol. 1994 Nov; 68(11): 7092–7098.
PMCID: PMC237147

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


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.

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Selected References

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  • 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. [PubMed]
  • Bachrach HL. Foot-and-mouth disease. Annu Rev Microbiol. 1968;22:201–244. [PubMed]
  • Bahnemann HG. Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production. Arch Virol. 1975;47(1):47–56. [PubMed]
  • Barnett PV, Ouldridge EJ, Rowlands DJ, Brown F, Parry NR. 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. [PubMed]
  • 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. [PubMed]
  • Baxt B, Morgan DO, Robertson BH, Timpone CA. 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. [PMC free article] [PubMed]
  • Baxt B, Vakharia V, Moore DM, Franke AJ, Morgan DO. Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus. J Virol. 1989 May;63(5):2143–2151. [PMC free article] [PubMed]
  • Bittle JL, Houghten RA, Alexander H, Shinnick TM, Sutcliffe JG, Lerner RA, Rowlands DJ, 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. [PubMed]
  • 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. [PubMed]
  • Cowan KM, Graves JH. A third antigenic component associated with foot-and-mouth disease infection. Virology. 1966 Nov;30(3):528–540. [PubMed]
  • 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 Aug;74(Pt 8):1547–1553. [PubMed]
  • 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. [PubMed]
  • Doel TR, Gale C, Do Amaral CM, 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. [PMC free article] [PubMed]
  • Fox G, Parry NR, Barnett PV, McGinn B, Rowlands DJ, 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. [PubMed]
  • Francis MJ, Hastings GZ, Clarke BE, Brown AL, Beddell CR, Rowlands DJ, 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]
  • Gebauer F, de la Torre JC, Gomes I, Mateu MG, Barahona H, Tiraboschi B, Bergmann I, de Mello PA, 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. [PMC free article] [PubMed]
  • Higuchi R, Krummel B, Saiki RK. 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. [PMC free article] [PubMed]
  • Kitson JD, Burke KL, Pullen LA, Belsham GJ, Almond JW. 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. [PMC free article] [PubMed]
  • 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 Nov;179(1):26–34. [PubMed]
  • Krebs O, Ahl R, Straub OC, 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. [PubMed]
  • Lea S, Hernández J, Blakemore W, Brocchi E, Curry S, Domingo E, Fry E, Abu-Ghazaleh R, King A, Newman J, et al. The structure and antigenicity of a type C foot-and-mouth disease virus. Structure. 1994 Feb 15;2(2):123–139. [PubMed]
  • Logan D, Abu-Ghazaleh R, Blakemore W, Curry S, Jackson T, King A, Lea S, Lewis R, Newman J, Parry N, et al. Structure of a major immunogenic site on foot-and-mouth disease virus. Nature. 1993 Apr 8;362(6420):566–568. [PubMed]
  • Makoff AJ, Paynter CA, Rowlands DJ, Boothroyd JC. 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. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Mason PW, 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. [PMC free article] [PubMed]
  • Mateu MG, Da Silva JL, Rocha E, De Brum DL, 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. [PubMed]
  • Mateu MG, Hernández J, Martínez MA, Feigelstock D, Lea S, Pérez JJ, Giralt E, Stuart D, Palma EL, 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. [PMC free article] [PubMed]
  • Mateu MG, Martínez MA, 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. [PMC free article] [PubMed]
  • Mateu MG, Martínez MA, 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. [PubMed]
  • Minor PD, Ferguson M, Katrak K, Wood D, John A, Howlett J, Dunn G, Burke K, Almond JW. 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. [PubMed]
  • Murdin AD, 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. [PMC free article] [PubMed]
  • Murray MG, Kuhn RJ, 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. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Pfaff E, Thiel HJ, Beck E, Strohmaier K, Schaller H. Analysis of neutralizing epitopes on foot-and-mouth disease virus. J Virol. 1988 Jun;62(6):2033–2040. [PMC free article] [PubMed]
  • Piccone ME, Kaplan G, Giavedoni L, Domingo E, Palma EL. VP1 of serotype C foot-and-mouth disease viruses: long-term conservation of sequences. J Virol. 1988 Apr;62(4):1469–1473. [PMC free article] [PubMed]
  • Rieder E, Bunch T, Brown F, Mason PW. 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. [PMC free article] [PubMed]
  • Robertson BH, Grubman MJ, Weddell GN, Moore DM, Welsh JD, Fischer T, Dowbenko DJ, Yansura DG, Small B, Kleid DG. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J Virol. 1985 Jun;54(3):651–660. [PMC free article] [PubMed]
  • Rueckert RR, Wimmer E. Systematic nomenclature of picornavirus proteins. J Virol. 1984 Jun;50(3):957–959. [PMC free article] [PubMed]
  • Salt JS. The carrier state in foot and mouth disease--an immunological review. Br Vet J. 1993 May-Jun;149(3):207–223. [PubMed]
  • Stave JW, Card JL, Morgan DO, Vakharia VN. 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. [PubMed]
  • Thomas AA, Woortmeijer RJ, Puijk W, Barteling SJ. Antigenic sites on foot-and-mouth disease virus type A10. J Virol. 1988 Aug;62(8):2782–2789. [PMC free article] [PubMed]
  • 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 Jun;68(Pt 6):1637–1647. [PubMed]

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