Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Apr 1997; 71(4): 2606–2614.
PMCID: PMC191381

A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants.

Abstract

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease. Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented. Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined. None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40%. Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus. In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified. This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo. In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy. Possible modifications of the vaccine formulations to increase protective activity are discussed.

Full Text

The Full Text of this article is available as a PDF (106K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • ANDERER FA, SCHLUMBERGER HD. PROPERTIES OF DIFFERENT ARTIFICIAL ANTIGENS IMMUNOLOGICALLY RELATED TO TOBACCO MOSAIC VIRUS. Biochim Biophys Acta. 1965 Mar 8;97:503–509. [PubMed]
  • Arnon R, Maron E, Sela M, Anfinsen CB. Antibodies reactive with native lysozyme elicited by a completely synthetic antigen. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1450–1455. [PMC free article] [PubMed]
  • Arnon R, Sela M. Antibodies to a unique region in lysozyme provoked by a synthetic antigen conjugate. Proc Natl Acad Sci U S A. 1969 Jan;62(1):163–170. [PMC free article] [PubMed]
  • Atassi MZ, Webster RG. Localization, synthesis, and activity of an antigenic site on influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1983 Feb;80(3):840–844. [PMC free article] [PubMed]
  • Bachrach HL. Foot-and-mouth disease. Annu Rev Microbiol. 1968;22:201–244. [PubMed]
  • Bachrach HL, Morgan DO, Moore DM. Foot-and-mouth disease virus immunogenic capsid protein VPT: N-terminal sequences and immunogenic peptides obtained by CNBr and tryptic cleavages. Intervirology. 1979;12(2):65–72. [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]
  • Barteling SJ, Vreeswijk J. Developments in foot-and-mouth disease vaccines. Vaccine. 1991 Feb;9(2):75–88. [PubMed]
  • Barteling SJ, Woortmeyer R. Multiple variants in foot-and-mouse disease virus (FMDV) populations: the Achilles heel for peptide and rec. DNA vaccines? Dev Biol Stand. 1987;66:511–521. [PubMed]
  • Beck E, Strohmaier K. Subtyping of European foot-and-mouth disease virus strains by nucleotide sequence determination. J Virol. 1987 May;61(5):1621–1629. [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]
  • Borras-Cuesta F, Petit-Camurdan A, Fedon Y. Engineering of immunogenic peptides by co-linear synthesis of determinants recognized by B and T cells. Eur J Immunol. 1987 Aug;17(8):1213–1215. [PubMed]
  • Borrego B, Camarero JA, Mateu MG, Domingo E. A highly divergent antigenic site of foot-and-mouth disease virus retains its immunodominance. Viral Immunol. 1995;8(1):11–18. [PubMed]
  • Brown F. New approaches to vaccination against foot-and-mouth disease. Vaccine. 1992;10(14):1022–1026. [PubMed]
  • Carreño C, Roig X, Cairo J, Camarero J, Mateu MG, Domingo E, Giralt E, Andreu D. Studies on antigenic variability of C strains of foot-and-mouth disease virus by means of synthetic peptides and monoclonal antibodies. Int J Pept Protein Res. 1992 Jan;39(1):41–47. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Collen T, Doel TR. Heterotypic recognition of foot-and-mouth disease virus by cattle lymphocytes. J Gen Virol. 1990 Feb;71(Pt 2):309–315. [PubMed]
  • Collen T, Dimarchi R, Doel TR. A T cell epitope in VP1 of foot-and-mouth disease virus is immunodominant for vaccinated cattle. J Immunol. 1991 Jan 15;146(2):749–755. [PubMed]
  • Cox JH, Ivanyi J, Young DB, Lamb JR, Syred AD, Francis MJ. Orientation of epitopes influences the immunogenicity of synthetic peptide dimers. Eur J Immunol. 1988 Dec;18(12):2015–2019. [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]
  • Domingo E. RNA virus evolution and the control of viral disease. Prog Drug Res. 1989;33:93–133. [PubMed]
  • Domingo E, Escarmis C, Martinez MA, Martinez-Salas E, Mateu MG. Foot-and-mouth disease virus populations are quasispecies. Curr Top Microbiol Immunol. 1992;176:33–47. [PubMed]
  • Domingo E, Dávila M, Ortín J. Nucleotide sequence heterogeneity of the RNA from a natural population of foot-and-mouth-disease virus. Gene. 1980 Nov;11(3-4):333–346. [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, Fry CM, Rowlands DJ, Bittle JL, Houghten RA, Lerner RA, Brown F. Immune response to uncoupled peptides of foot-and-mouth disease virus. Immunology. 1987 May;61(1):1–6. [PMC free article] [PubMed]
  • Francis MJ, Hastings GZ, Syred AD, McGinn B, Brown F, Rowlands DJ. Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants. Nature. 1987 Nov 12;330(6144):168–170. [PubMed]
  • Glass EJ, Oliver RA, Collen T, Doel TR, Dimarchi R, Spooner RL. MHC class II restricted recognition of FMDV peptides by bovine T cells. Immunology. 1991 Dec;74(4):594–599. [PMC free article] [PubMed]
  • Glass EJ, Millar P. Bovine T cells preferentially recognize non-viral spacer epitopes in a putative FMDV vaccinal peptide. Vaccine. 1995 Feb;13(2):225–229. [PubMed]
  • Golvano J, Lasarte JJ, Sarobe P, Gullón A, Prieto J, Borrás-Cuesta F. Polarity of immunogens: implications for vaccine design. Eur J Immunol. 1990 Oct;20(10):2363–2366. [PubMed]
  • Green N, Alexander H, Olson A, Alexander S, Shinnick TM, Sutcliffe JG, Lerner RA. Immunogenic structure of the influenza virus hemagglutinin. Cell. 1982 Mar;28(3):477–487. [PubMed]
  • Kaaden OR, Adam KH, Strohmeier K. Induction of neutralizing antibodies and immunity in vaccinated guinea pigs by cyanogen bromide-peptides of VP3 of foot-and-mouth disease virus. J Gen Virol. 1977 Feb;34(2):397–400. [PubMed]
  • Kleid DG, Yansura D, Small B, Dowbenko D, Moore DM, Grubman MJ, McKercher PD, Morgan DO, Robertson BH, Bachrach HL. Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine. Science. 1981 Dec 4;214(4525):1125–1129. [PubMed]
  • Küpper H, Keller W, Kurz C, Forss S, Schaller H, Franze R, Strohmaier K, Marquardt O, Zaslavsky VG, Hofschneider PH. Cloning of cDNA of major antigen of foot and mouth disease virus and expression in E. coli. Nature. 1981 Feb 12;289(5798):555–559. [PubMed]
  • Lerner RA, Green N, Alexander H, Liu FT, Sutcliffe JG, Shinnick TM. Chemically synthesized peptides predicted from the nucleotide sequence of the hepatitis B virus genome elicit antibodies reactive with the native envelope protein of Dane particles. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3403–3407. [PMC free article] [PubMed]
  • Martínez MA, Hernández J, Piccone ME, Palma EL, Domingo E, Knowles N, Mateu MG. Two mechanisms of antigenic diversification of foot-and-mouth disease virus. Virology. 1991 Oct;184(2):695–706. [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. Antibody recognition of picornaviruses and escape from neutralization: a structural view. Virus Res. 1995 Sep;38(1):1–24. [PubMed]
  • Mateu MG, Andreu D, Domingo E. Antibodies raised in a natural host and monoclonal antibodies recognize similar antigenic features of foot-and-mouth disease virus. Virology. 1995 Jun 20;210(1):120–127. [PubMed]
  • Mateu MG, Camarero JA, Giralt E, Andreu D, Domingo E. Direct evaluation of the immunodominance of a major antigenic site of foot-and-mouth disease virus in a natural host. Virology. 1995 Jan 10;206(1):298–306. [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, 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]
  • Mateu MG, Rocha E, Vicente O, Vayreda F, Navalpotro C, Andreu D, Pedroso E, Giralt E, Enjuanes L, Domingo E. Reactivity with monoclonal antibodies of viruses from an episode of foot-and-mouth disease. Virus Res. 1987 Sep;8(3):261–274. [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]
  • McCullough KC, De Simone F, Brocchi E, Capucci L, Crowther JR, Kihm U. Protective immune response against foot-and-mouth disease. J Virol. 1992 Apr;66(4):1835–1840. [PMC free article] [PubMed]
  • Meyer RF, Pacciarini M, Hilyard EJ, Ferrari S, Vakharia VN, Donini G, Brocchi E, Molitor TW. Genetic variation of foot-and-mouth disease virus from field outbreaks to laboratory isolation. Virus Res. 1994 Jun;32(3):299–312. [PubMed]
  • Morgan DO, Moore DM. Protection of cattle and swine against foot-and-mouth disease, using biosynthetic peptide vaccines. Am J Vet Res. 1990 Jan;51(1):40–45. [PubMed]
  • Mulcahy G, Gale C, Robertson P, Iyisan S, DiMarchi RD, Doel TR. Isotype responses of infected, virus-vaccinated and peptide-vaccinated cattle to foot-and-mouth disease virus. Vaccine. 1990 Jun;8(3):249–256. [PubMed]
  • Müller GM, Shapira M, Arnon R. Anti-influenza response achieved by immunization with a synthetic conjugate. Proc Natl Acad Sci U S A. 1982 Jan;79(2):569–573. [PMC free article] [PubMed]
  • Pfaff E, Mussgay M, Böhm HO, Schulz GE, Schaller H. Antibodies against a preselected peptide recognize and neutralize foot and mouth disease virus. EMBO J. 1982;1(7):869–874. [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]
  • Pinto AA, Garland AJ. Immune response to virus-infection-associated (VIA) antigen in cattle repeatedly vaccinated with foot-and-mouth disease virus inactivated by formalin or acetylethyleneimine. J Hyg (Lond) 1979 Feb;82(1):41–50. [PMC free article] [PubMed]
  • Rodríguez A, Sáiz JC, Novella IS, Andreu D, Sobrino F. Antigenic specificity of porcine T cell response against foot-and-mouth disease virus structural proteins: identification of T helper epitopes in VP1. Virology. 1994 Nov 15;205(1):24–33. [PubMed]
  • Rowlands DJ, Clarke BE, Carroll AR, Brown F, Nicholson BH, Bittle JL, Houghten RA, Lerner RA. Chemical basis of antigenic variation in foot-and-mouth disease virus. Nature. 1983 Dec 15;306(5944):694–697. [PubMed]
  • Sáiz JC, Rodríguez A, González M, Alonso F, Sobrino F. Heterotypic lymphoproliferative response in pigs vaccinated with foot-and-mouth disease virus. Involvement of isolated capsid proteins. J Gen Virol. 1992 Oct;73(Pt 10):2601–2607. [PubMed]
  • Sáiz JC, Sobrino F, Dopazo J. Molecular epidemiology of foot-and-mouth disease virus type O. J Gen Virol. 1993 Oct;74(Pt 10):2281–2285. [PubMed]
  • Shaw DM, Stanley CM, Partidos CD, Steward MW. Influence of the T-helper epitope on the titre and affinity of antibodies to B-cell epitopes after co-immunization. Mol Immunol. 1993 Aug;30(11):961–968. [PubMed]
  • Schwartz RH. The value of synthetic peptides as vaccines for eliciting T-cell immunity. Curr Top Microbiol Immunol. 1986;130:79–85. [PubMed]
  • Strohmaier K, Franze R, Adam KH. Location and characterization of the antigenic portion of the FMDV immunizing protein. J Gen Virol. 1982 Apr;59(Pt 2):295–306. [PubMed]
  • Van Lierop MJ, Nilsson PR, Wagenaar JP, Van Noort JM, Campbell JD, Glass EJ, Joosten I, Hensen EJ. The influence of MHC polymorphism on the selection of T-cell determinants of FMDV in cattle. Immunology. 1995 Jan;84(1):79–85. [PMC free article] [PubMed]
  • van Lierop MJ, Wagenaar JP, van Noort JM, Hensen EJ. Sequences derived from the highly antigenic VP1 region 140 to 160 of foot-and-mouth disease virus do not prime for a bovine T-cell response against intact virus. J Virol. 1995 Jul;69(7):4511–4514. [PMC free article] [PubMed]
  • Verdaguer N, Mateu MG, Andreu D, Giralt E, Domingo E, Fita I. Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg-Gly-Asp motif in the interaction. EMBO J. 1995 Apr 18;14(8):1690–1696. [PMC free article] [PubMed]
  • Walter G, Scheidtmann KH, Carbone A, Laudano AP, Doolittle RF. Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5197–5200. [PMC free article] [PubMed]
  • Weidt G, Deppert W, Utermöhlen O, Heukeshoven J, Lehmann-Grube F. Emergence of virus escape mutants after immunization with epitope vaccine. J Virol. 1995 Nov;69(11):7147–7151. [PMC free article] [PubMed]

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

Formats:

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...