title: Analysis of the immune response against mixotope peptide libraries from a main antigenic site of foot-and-mouth disease virus.
abstract: The design of vaccines for RNA viral diseases is complicated by the high genetic variability of the viruses, which favors the selection of escape mutants. A case in point is foot-and-mouth disease virus (FMDV), for which only limited protection has been observed in vaccination with single peptides. We have explored the potential of immunogens of higher sequence diversity, covering a broad range of field or culture-induced mutations at the immunodominant site A of FMDV, serotype C. Four mixotope-type peptide libraries, containing ca. 3 x 10(3) or ca. 3 x 10(5) peptides each, in either linear or cyclic form, and combining most significant mutations found or induced at site A have been synthesized and used to immunize guinea-pigs. Substantial levels of serum conversion have been observed for all four mixotope libraries, as well as for single peptides, linear or cyclic, corresponding to the consensus site A sequence. The specificity and neutralizing ability of the anti-mixotope and -peptide antibodies have been evaluated by direct ELISA and by plaque reduction and micro-neutralization assays, respectively. Challenge experiments with an infectious, guinea-pig-adapted FMDV strain, have shown higher protection rates in animals immunized with the cyclic versions, either in single sequence or in combinatorial mixotope form.
authors.affiliation: Department of Experimental and Health Sciences, Pompeu Fabra University, Dr. Aiguader 80, 08003 Barcelona, Spain.
authors.forename: Eliandre de
authors.initials: Ed
authors.lastname: Oliveira
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Jiménez-Clavero
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Núñez
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
authors.forename: David
authors.initials: D
authors.lastname: Andreu
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis*; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D006168:Guinea Pigs; D008297:Male; D009500:Neutralization Tests; D019151:Peptide Library; D022223:Vaccines, Subunit / Q000138:chemical synthesis* / Q000276:immunology*; D010948:Viral Plaque Assay
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019151:Peptide Library; D022223:Vaccines, Subunit