Compositions and methods for reducing serum triglycerides
An immunogen generally includes a virus-like particle and an antigen linked to the virus-like particle. The antigen includes an antigenic portion of a polypeptide, wherein the polypeptide inhibits lipoprotein lipase (LPL) activity by binding to LPL. In some embodiments, the polypeptide is at least a portion of angiopoietin-like 3 (ANGPTL3). In other embodiments, the polypeptide is at least a portion of angiopoietin-like 4 (ANGPTL4). In other embodiments, the polypeptide at least a portion of angiopoietin-like 8 (ANGPTL8). In some embodiments, the virus-like particle is a Qbeta immunogenic carrier. In some of these embodiments, the antigen is linked to the virus-like particle through a Gly-Gly-Gly-Cys linker at the C-terminal of the antigen.
1. An immunogen comprising:
a virus-like particle; and
an antigen linked to the virus-like particle, the antigen comprising an antigenic portion of SEQ ID NO:1.
2. The immunogen of claim 1 , wherein the antigen comprises an amino acid sequence having at least 80% sequence similarity to amino acids 32-47 of SEQ ID NO:1.
3. The immunogen of claim 1 , wherein the antigen comprises an amino acid sequence having at least 80% sequence similarity to amino acids 32-57 of SEQ ID NO:1.
4. The immunogen of claim 1 , wherein the virus-like particle comprises one or more Qbeta coat proteins.
5. The immunogen of claim 4 , wherein the antigen is linked to the VLP through a Gly-Gly-Gly-Cys (SEQ ID NO:6) linker at the C-terminal of the antigen.
6. A composition comprising:
the immunogen of claim 1 ; and
a pharmaceutically-acceptable carrier.
7. The composition of claim 6 , further comprising an adjuvant.
8. A method of reducing serum triglycerides in a subject, the method comprising administering a therapeutically effective amount of the immunogen of claim 1 to the subject.
9. The method of claim 8 , wherein the immunogen is administered in combination with an adjuvant.
10. The method of claim 8 , wherein the immunogen is administered in combination with at least one additional therapeutic agent.
11. The method of claim 10 , wherein the additional therapeutic agent comprises a statin or a fibric acid derivative.
12. A nucleic acid encoding the immunogen of claim 1 .
13. An expression vector comprising the nucleic acid of claim 12 .
14. A host cell comprising the expression vector of claim 13 .