The filamentous phage as a multivalent scaffold for coupling...

C - Chemistry – Metallurgy – 12 – N

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C12N 7/01 (2006.01) A61K 38/17 (2006.01) A61K 39/385 (2006.01) C07H 21/04 (2006.01) C07K 14/245 (2006.01) C07K 14/435 (2006.01) C07K 14/445 (2006.01) C12N 5/10 (2006.01) C12N 15/10 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2286301

The filamentous bacteriophage is a common immunogenic carrier for generating anti-peptide antibodies against recombinant peptides displayed on its surface. For immunizations, peptides are displayed as fusions to either the minor coat protein, pIII, or, more commonly the major coat protein, pVIII. Phage displaying a poorly expressed malarial peptide on pVIII were compared to phage bearing the same peptide on pIII , and to phage that were chemically coupled to a synthetic version of the peptide using the crosslinker, sulfo-succinimidyl 4-(N-maleimido-methyl)cyclohexane-1-carboxylate (sulfo-SMCC) for their ability to induce an anti-peptide Ab response in mice. We also included in this comparison the same peptide displayed as a recombinant fusion to the maltose-binding protein (MBP) of Escherichia coli, as well as the synthetic counterpart as chemically crosslinked to MBP with sulfo-SMCC. The results demonstrate that only the chemically-crosslinked conjugates elicited a strong anti-peptide antibody response by ELISA, probably due to the higher number of peptides that were displayed by the phage and MBP conjugates as compared to their recombinant counterparts. The amount of peptide that was covalently linked to the phage was increased approximately two-fold when a lysine residue was engineered near the N-terminus of mature pVIII. The ease of chemically conjugating synthetic peptides to phage, and of modifying pVIII by genetic engineering, suggests new roles for the filamentous phage in vaccine studies.

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