Neutralizing GDF8 epitope-based growth enhancing vaccine
View Patent ↗The invention provides new, specific antigenic peptides from the protein GDF8. The invention also provides fusion proteins comprising the new peptides, immunogens and vaccines based on the new peptides and/or fusion proteins, antibodies that specifically bind to the new peptides of GDF8, and methods of treating animals in order to modulate the activity of GDF8, employing vaccines or antibodies according to the invention.
1. An isolated peptide consisting of 50 or fewer amino acid residues that comprises amino acid residues 327 to 346 of SEQ ID NO:1.
2. The isolated peptide of claim 1 that comprises amino acid residues 321 to 346 of SEQ ID NO:1.
3. The isolated peptide of claim 2 that comprises amino acid residues 320 to 350 of SEQ ID NO:1.
4. The isolated peptide of claim 3 that comprises amino acid residues 312 to residue 361 of SEQ ID NO:1.
5. An isolated peptide consisting of 50 or fewer amino-acid residues that comprises amino acid residues 327 to 346 of SEQ ID NO:1 comprising an amino acid substitution;
wherein there are no more than five amino acid substitutions between amino acid residues 327 to residue 346; and
wherein the peptide specifically binds to rat monoclonal antibody 788.
6. The isolated peptide of claim 5 comprising amino acid substitutions at a position selected from the group consisting of residues 328, 329, 331, 333 and 335, and combinations thereof,
wherein,
(a) amino acid residue 328 is His, Leu, or Asn;
(b) amino acid residue 329 is Gln or Lys;
(c) amino acid residue 331 is Asn or Ser;
(d) amino acid residue 333 is Arg or Lys; and/or
(e) amino acid residue 335 is Ser, Pro, or Thr.
7. The isolated peptide of claim 6 comprising no more than one amino acid substitution between residues 327 to residue 346 of the precursor GDF8, provided that the peptide specifically binds to rat monoclonal antibody 788.
8. The isolated peptide of claim 1 that comprises a specific neutralization epitope for an anti-GOF8 antibody.
9. The isolated peptide of claim 8 , wherein the antibody is selected from the group consisting of rat anti-GDF8 monoclonal antibody 788 and an lgG fraction of goat anti-GDF8 polyclonal antiserum.
10. A fusion protein comprising the peptide of claim 1 or an antigenic subfragment of the peptide.
11. A vaccine composition comprising the peptide of claim 1 .
12. A vaccine composition comprising the fusion protein of claim 10 .
13. The vaccine composition of claim 11 further comprising an adjuvant.
14. A method of eliciting an anti-GDF8 immune response in an animal, comprising administering to the animal an effective amount of the vaccine composition of claim 11 .
15. A screening method for selecting an anti-GDF8 antibody or antibody fragment from among a plurality of antibodies or antibody fragments, comprising contacting the peptide of claim 1 with a sample comprising one or a plurality of antibodies or antibody fragments, and detecting antibody or antibody fragment that selectively binds to the peptide.
16. A method of down-regulating GDF8 activity in an animal comprising administering an antibody or antibody fragment to the animal, in an amount and for a duration effective to down-regulate GDF8 activity in the animal, wherein the antibody binds specifically to the peptide of claim 1 .
17. A method of down-regulating GDF8 activity in an animal comprising immunizing the animal with an effective amount of the vaccine composition of claim 11 .
18. A method of down-regulating GDF8 activity in an animal comprising immunizing the animal with an effective amount of the vaccine composition of claim 12 .