Analysis of the immune response against mixotope peptide libraries from a main antigenic site of foot-and-mouth disease virus.
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.
Oliveira
Eliandre de
Ed
Department of Experimental and Health Sciences, Pompeu Fabra University, Dr. Aiguader 80, 08003 Barcelona, Spain.
Jiménez-Clavero
Miguel Angel
MA
Núñez
José Ignacio
JI
Sobrino
Francisco
F
Andreu
David
D
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
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019151:Peptide Library; D022223:Vaccines, Subunit