B epitope multiplicity and B/T epitope orientation influence immunogenicity of foot-and-mouth disease peptide vaccines.
Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFN γ . Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain.
Esther
E
Blanco
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain.
Carolina
C
Cubillos
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain.
Noelia
N
Moreno
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain.
Juan
J
Bárcena
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Beatriz G
BG
de la Torre
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
David
D
Andreu
Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain ; Centro de Biología Molecular, "Severo Ochoa" (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain.
Francisco
F
Sobrino
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000145:classification / Q000276:immunology*; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010455:Peptides; D022223:Vaccines, Subunit; D014765:Viral Vaccines; D007371:Interferon-gamma