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 a transmembrane modified gH polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:16.
2. The VLP of claim 1 , wherein the second polypeptide comprises an amino acid sequence that is at least 97% identical to SEQ ID NO:16.
3. The VLP of claim 1 , wherein the second polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO:16.
4. The VLP of claim 1 , wherein the second polypeptide comprises the amino acid sequence of SEQ ID NO:16.
5. The VLP of claim 1 , further comprising a third polypeptide comprising a gB polypeptide.
6. The VLP of claim 5 , wherein the third polypeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO:7.
7. The VLP of claim 5 , wherein the gB polypeptide is a transmembrane modified gB polypeptide.
8. The VLP of claim 7 , wherein the transmembrane modified gB polypeptide comprises a transmembrane domain found in nature in a vesicular stomatitis virus (VSV) protein.
9. The VLP of claim 8 , wherein the transmembrane modified gB polypeptide comprises an amino acid sequence at least 85% identical to SEQ ID NO:10.
10. A transmembrane modified gH polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:16.
11. The transmembrane modified gH polypeptide of claim 10 , comprising an amino acid sequence at least 97% identical to SEQ ID NO:16.
12. The transmembrane modified gH polypeptide of claim 10 , comprising an amino acid sequence at least 99% identical to SEQ ID NO:16.
13. The transmembrane modified gH polypeptide of claim 10 , comprising the amino acid sequence of SEQ ID NO:16.
14. A virus-like particle (VLP) comprising the polypeptide of claim 10 .
15. A vector comprising a nucleotide sequence encoding the polypeptide of claim 10 .
16. A method for the production of a virus-like particle (VLP), the method comprising:
co-transfecting a host cell with:
a first vector comprising a nucleotide sequence encoding a 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 vector comprising a nucleotide sequence encoding a polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:16; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the polypeptides encoded by the vectors.
17. 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 a pharmaceutical composition comprising the VLP of claim 1 .