title: A protective anti-peptide antibody against the immunodominant site of the A24 Cruzeiro strain of foot-and-mouth disease virus and its reactivity with other subtype viruses containing the same minimum binding sequence.
abstract: A synthetic peptide vaccine of the general sequence Cys-Cys-(200-213)-Pro-Pro-Ser-(l41-158)-Pro-Cys-Gly(peptide A40), where the numbered residues refer to the VP1 sequence of foot-and-mouth disease virus (FMDV) strain A24 Cruzeiro, has previously been shown to elicit neutralizing and protective antibodies in guinea-pigs and cattle. To examine this immunogenic tract in more detail monoclonal antibodies (MAbs) were raised to this peptide. One such MAb C1.1, which recognized the homologous peptide, bound to native virus, neutralized infectivity in vitro and passively protected mice from challenge. Using overlapping dodecameric peptides the minimum binding 'footprint' of this MAb incorporated residues 149-154 which were respectively Gly-Ser-Leu-Ala-Ala-Arg. Since this 'footprint' occurs in several other A subtype strains of FMDV, the extent to which MAb C1.1 could cross-react was also examined. Using a liquid-phase competition ELISA, only viruses with a sequence that encompassed the same minimum binding 'footprint', namely A27 Cundinamarca Colombia/76, A Argentina/79, and A Venceslau Brazil/76 reacted with similar affinity against MAb C1.1. However, further serological examination of C1.1 with these viruses by indirect ELISA, in vitro neutralization and passive protection showed clear functional disparity. In contrast to the liquid-phase ELISA, the ability of C1.1 to react with electrostatically bound virus varied significantly depending on the subtype examined. Moreover, the capacity of this MAb to neutralize these subtypes showed wide divergence which was mirrored by the protection data.
authors.affiliation: Institute for Animal Health, Pirbright Laboratory, Woking, Surrey, UK.
authors.forename: P V
authors.initials: PV
authors.lastname: Barnett
authors.forename: L
authors.initials: L
authors.lastname: Pullen
authors.forename: R F
authors.initials: RF
authors.lastname: Staple
authors.forename: L J
authors.initials: LJ
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Butcher
authors.forename: D
authors.initials: D
authors.lastname: Parkinson
authors.forename: T R
authors.initials: TR
authors.lastname: Doel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D002460:Cell Line; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D010446:Peptide Fragments; C442501:VP1 protein, Foot-and-mouth disease virus; D014614:Vaccines, Synthetic