Influence of conjugation chemistry and B epitope orientation on the immune response of branched peptide antigens
Multimeric presentation, a well-proven way of enhancing peptide immunogenicity, has found substantial application in synthetic vaccine design. We have reported that a combination of four copies of a B-cell epitope with one of a T-cell epitope in a single branched construct results in a peptide vaccine conferring total protection against foot-and-mouth disease virus in swine, a natural host (Cubillos et al. (2008) J. Virol.82, 7223-7230). More recently, a downsized version of this prototype with only two copies of the B epitope has proven as effective as the tetravalent one in mice. Here we evaluate three approaches to bivalent platforms of this latter type, involving different chemistries for the conjugation of two B epitope peptides to a branching T epitope. Comparison of classical thioether, "reverse" thioether (Monsó et al. (2012) Org. Biomol. Chem. 10, 3116-3121) and thiol-ene conjugation chemistries in terms of synthetic efficiency clearly singles out the latter, maleimide-based strategy as most advantageous. We also examine how minor structural differences among the conjugates -including the N-or C-terminal attachment of the B epitope to the branching T epitope -bear on the immunogenicity of these vaccine candidates, with the maleimide-based conjugate again emerging as the most successful. © 2013 American Chemical Society.
| Main Authors: | , , , , |
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| Format: | journal article biblioteca |
| Language: | English |
| Published: |
American Chemical Society
2013
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| Online Access: | http://hdl.handle.net/20.500.12792/2927 http://hdl.handle.net/10261/294178 |
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