BoNT/A peptides and methods of predicting and reducing immunoresistance to botulinum toxin therapy
The present invention provides BoNT/A peptides as well as methods of predicting or determining immunoresistance to botulinum toxin therapy in an individual using BoNT/A peptides.
1. A tolerogizing composition capable of inducing a specific immunological tolerance to a botulinum toxin antigen, said tolerogizing composition comprising a tolerogizing agent conjugated to a BoNT/A peptide;
wherein 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 immunolocical 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; and
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.
2. The tolerogizing composition of claim 1 , wherein said BoNT/A peptide comprises amino acids 771-789 of SEQ ID NO: 1, or amino acids 785-803 of SEQ ID NO: 1.
3. The tolerogizing composition of claim 1 , wherein said BoNT/A peptide comprises 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 conservative BoNT/A amino acid sequence variant producing a decreased immunological response comprises 1-4 conservative amino acid substitutions to amino acids 785-803 of SEQ ID NO: 1; and
wherein said tolerogenic BoNT/A amino acid sequence fragment producing a decreased immunological response comprises at least six consecutive amino acids of 785-803 of SEQ ID NO: 1.
4. The tolerogizing composition of claim 3 , wherein said BoNT/A peptide comprises amino acids 785-803 of SEQ ID NO: 1.
5. The tolerogizing composition of claim 1 , wherein said BoNT/A peptide comprises amino acids 771-789 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 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; and
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.
6. The tolerogizing composition of claim 5 , wherein said BoNT/A peptide comprises amino acids 771-789 of SEQ ID NO: 1.
7. The tolerogizing composition of claim 1 , wherein said BoNT/A peptide is at most 40 amino acids in length.
8. The tolerogizing composition of claim 1 , wherein said BoNT/A peptide is at most 25 amino acids in length.
9. The tolerogizing composition of claim 1 , wherein said tolerogizing agent is a polyethylene glycol.
10. The tolerogizing composition of claim 1 , wherein said tolerogizing agent is a monomethoxypolyethylene glycol.
11. The tolerogizing composition of claim 1 , wherein said tolerogizing agent is a polyvinyl alcohol.