B epitope multiplicity and B/T epitope orientation influence immunogenicity of foot-and-mouth disease peptide vaccines

Clin Dev Immunol. 2013:2013:475960. doi: 10.1155/2013/475960. Epub 2013 Dec 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antibody Specificity / immunology
  • Epitopes, B-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Foot-and-Mouth Disease / immunology*
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease Virus / classification
  • Foot-and-Mouth Disease Virus / immunology*
  • Immunity, Humoral
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Interferon-gamma / biosynthesis
  • Mice
  • Peptides / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Vaccines, Subunit / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Immunoglobulin A
  • Immunoglobulin G
  • Peptides
  • Vaccines, Subunit
  • Viral Vaccines
  • Interferon-gamma