Compositions and methods for treatment of cytomegalovirus
View Patent ↗The present disclosure provides compositions and methods useful for treating HCMV infection. As described herein, the compositions and methods are based on development of immunogenic compositions that include virus-like particles (VLPs) which comprise one or more Moloney Murine leukemia virus (MMLV) core proteins and include one or more HCMV epitopes, such as, for example, from HCMV envelope glycoproteins gB and/or gH and/or tegument protein pp65. Among other things, the present invention encompasses the recognition that a combination of antigens (e.g., envelope glycoproteins and structural proteins) can lead to beneficial immune responses, for example that include both a humoral response (e.g., production of neutralizing antibodies) and a cellular response (e.g., T-cell activation).
1. A virus like particle (VLP) comprising:
a fusion protein comprising an N-terminal portion of a gag protein found in a murine leukemia virus (MLV) fused upstream of a pp65 protein found in HCMV; and
a polypeptide comprising a glycoprotein (gB) protein found in HCMV.
2. The VLP of claim 1 , wherein the N-terminal portion of the gag protein does not comprise a C-terminal polymerase sequence found in MLV.
3. The VLP of claim 1 , wherein the N-terminal portion of the gag protein comprises the amino acid sequence of SEQ ID NO:1.
4. The VLP of claim 1 , wherein the N-terminal portion of the gag protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:1.
5. The VLP of claim 1 , wherein the polypeptide comprising the gB protein comprises the amino acid sequence of SEQ ID NO:7.
6. The VLP of claim 1 , wherein the polypeptide comprising the gB protein comprises at least 15 consecutive residues of SEQ ID NO:7.
7. The VLP of claim 1 , wherein the polypeptide comprising the gB protein comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:7.
8. A VLP comprising:
a fusion protein comprising an amino acid sequence at least 85% identical to SEQ ID NO:4.; and
a polypeptide comprising an amino acid sequence at least 85% identical to SEQ ID NO:7.
9. The VLP of claim 8 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO:4, and the polypeptide comprises the amino acid sequence of SEQ ID NO:7.
10. A pharmaceutical composition comprising the VLP of any one of claims 1 and 8 , and a pharmaceutically acceptable carrier.
11. The pharmaceutical composition of claim 10 , further comprising an adjuvant selected from the group consisting of a cytokine, a gel-type adjuvant, a microbial adjuvant, an oil-emulsion adjuvant, an emulsifier-based adjuvant, a particulate adjuvant, a synthetic adjuvant, a polymer adjuvant, and a combination thereof.
12. A method for the production of a VLP, the method comprising:
co-transfecting a host cell with a vector comprising a nucleotide sequence encoding an MLV gag-HCMV pp65 fusion protein, wherein the gag protein is fused upstream of the pp65 protein, and a vector comprising a nucleotide sequence encoding a gB polypeptide found in HCMV; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.
13. A method for reducing frequency or severity or delaying onset of symptoms of HCMV infection in a subject, the method comprising administering to the subject the pharmaceutical composition of claim 10 .