title: Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide.
abstract: Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have reported (Cubillos et al., 2008) that a synthetic dendrimeric peptide consisting of four copies of a B-cell epitope [VP1(136-154)] linked through thioether bonds to a T-cell epitope [3A(21-35)] of FMDV [B4T(thi)] elicits potent B- and T-cell specific responses and confers solid protection in pigs to type C FMDV challenge. Herein we show that downsized versions of this peptide bearing two copies of a B-cell epitope from a type O isolate and using thioether [B2T(thi)] or maleimide [B2T(mal)] conjugation chemistries for their synthesis elicited in swine similar or higher B and T-cell specific responses than tetravalent B4T(thi). Moreover, while partial protection was observed in animals immunized with B4T(thi) (60%) and B2T(thi) (80%), B2T(mal) conferred full (100%) protection against FMDV challenge, associated to high levels of circulating IgG2 and mucosal IgGA, and entirely prevented virus shedding. Interestingly, B2T(mal) is also the most advantageous option in terms of synthetic practicality. Taken together, the results reported here point out to B2T(mal) as a highly valuable, cost-effective FMDV candidate vaccine.
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain. Electronic address: blanco@inia.es.
authors.forename: Esther
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Guerra
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu-Fabra, 08003 Barcelona, Spain.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: de la Torre
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu-Fabra, 08003 Barcelona, Spain.
authors.forename: Sira
authors.initials: S
authors.lastname: Defaus
authors.affiliation: Central Veterinary Institute (CVI), Wageningen UR, 8200 AB Lelystad, The Netherlands.
authors.forename: Aldo
authors.initials: A
authors.lastname: Dekker
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu-Fabra, 08003 Barcelona, Spain. Electronic address: david.andreu@upf.edu.
authors.forename: David
authors.initials: D
authors.lastname: Andreu
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. Electronic address: fsobrino@cbm.csic.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D050091:Dendrimers / Q000138:chemical synthesis / Q000191:economics; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005536:Foot-and-Mouth Disease / Q000517:prevention & control* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology* / Q000472:pathogenicity; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma; D009297:Nasal Mucosa / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D013552:Swine; D013553:Swine Diseases / Q000517:prevention & control* / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000191:economics / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D057134:Antibodies, Neutralizing; D050091:Dendrimers; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010455:Peptides; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: Foot-and-mouth disease virus; Peptide dendrimers; Protection; Vaccines