Compositions and methods for treatment of cytomegalovirus
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 first polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:1; and
a second polypeptide comprising the amino acid sequence of SEQ ID NO:10.
2. The VLP of claim 1 , wherein the second polypeptide consists of the amino acid sequence of SEQ ID NO: 10.
3. The VLP of claim 1 , wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO: 1.
4. The VLP of claim 1 , wherein the first polypeptide consists of the amino acid sequence of SEQ ID NO: 1.
5. A pharmaceutical composition comprising the VLP of claim 1 and a pharmaceutically acceptable carrier.
6. The pharmaceutical composition of claim 5 , 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.
7. A method of producing a VLP, the method comprising:
co-transfecting a host cell with a vector comprising a nucleotide sequence encoding a first polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 and a vector comprising a nucleotide sequence encoding a second polypeptide comprising the amino acid sequence of SEQ ID NO: 10; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.
8. A method of 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 5 .
9. The VLP of claim 1 , wherein the first polypeptide comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 1.
10. The VLP of claim 1 , wherein the first polypeptide comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 1.
11. The VLP of claim 1 , wherein the first polypeptide comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 1.
12. The VLP of claim 1 , wherein the first polypeptide comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 1.
13. The method of claim 7 , wherein the first polypeptide comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 1.
14. The method of claim 7 , wherein the first polypeptide comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 1.
15. The method of claim 7 , wherein the first polypeptide comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 1.
16. The method of claim 7 , wherein the first polypeptide comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 1.
17. The method of claim 8 , wherein the first polypeptide comprises an amino acid sequence that is at least 96% identical to the amino acid sequence of SEQ ID NO: 1.
18. The method of claim 8 , wherein the first polypeptide comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO: 1.
19. The method of claim 8 , wherein the first polypeptide comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 1.
20. The method of claim 8 , wherein the first polypeptide comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 1.