Bont/a peptides and methodsof predicting and reducing immunoresistance to botulinum toxin therapy

A tolerogizing method of preventing or reducing immunoresistance to botulinum toxin therapy in an individual, the method comprising the step of administering to said individual a tolerogizing composition;

• wherein said tolerogizing composition comprising a tolerogizing agent conjugated to a BoNT/A peptide, said BoNT/A peptide is at most 60 amino acids in length and comprises amino acids 771-789 of SEQ ID NO:
• 1, amino acids 785-803 of SEQ ID NO:
• 1, a conservative BoNT/A amino acid sequence variant thereof, or a tolerogenic BoNT/A amino acid sequence fragment thereof;
• wherein said amino acids 771-789 of SEQ ID NO:
• 1, amino acids 785-803 of SEQ ID NO:
• 1, a conservative BoNT/A amino acid sequence variant thereof and a tolerogenic BoNT/A amino acid sequence fragment thereof produce a decrease in a humoral immunological response to a botulinum toxin antigen thereby inducing a specific immunological tolerance to the botulinum toxin antigen;
• wherein said conservative BoNT/A amino acid sequence variant producing a decreased immunological response comprises 1-4 conservative amino acid substitutions to amino acids 771-789 of SEQ ID NO:
• 1, or 1-4 conservative amino acid substitutions to amino acids 785-803 of SEQ ID NO:
• 1;
• wherein said tolerogenic BoNT/A amino acid sequence fragment producing a decreased immunological response comprises at least six consecutive amino acids of 771-789 of SEQ ID NO:
• 1, or at least six consecutive amino acids of 785-803 of SEQ ID NO:
• 1;
• and
• wherein administration of said tolerogizing composition decreases an immunological response to a botulinum toxin antigen.