VACCINE COMPOSITIONS FOR THE TREATMENT OF CORONAVIRUS
The present disclosure provides compositions and methods useful for preventing and/or treating coronavirus 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 a spike protein from the Beta variant of SARS-Cov-2.
1 . An immunogenic composition comprising a virus-like particle (VLP) comprising:
a first polypeptide that is a gag protein found in murine leukemia virus (MLV) having at least 95% identity with the amino acid sequence of SEQ ID NO:1;
at least one additional polypeptide which is a spike glycoprotein from the Beta variant of the SARS-CoV-2 coronavirus; and
a pharmaceutically acceptable carrier.
2 . The immunogenic composition of claim 1 wherein the spike glycoprotein is a modified protein.
3 . The immunogenic composition of claim 2 wherein the modified protein has a deletion at a furin cleavage site.
4 . The immunogenic composition of claim 2 wherein the modified protein has a transmembrane domain from VSV.
5 . The immunogenic composition of claim 2 wherein the modified protein has a lysine residue and a valine residue replaced with proline residues.
6 . The immunogenic composition of claim 5 wherein the modified protein has a transmembrane domain from VSV.
7 . The immunogenic composition of claim 2 wherein the modified protein has a lysine residue and a valine residue replaced with proline residues and has a deletion at a furin cleavage site.
8 . The immunogenic composition of claim 2 wherein the modified protein has a lysine residue and a valine residue replaced with proline residues and has a deletion at a furin cleavage site and has a transmembrane domain from VSV.
9 . The immunogenic composition of claim 1 , wherein the additional polypeptide has an amino acid sequence of SEQ ID NO: 28.
10 . The immunogenic composition of claim 1 , further comprising an adjuvant.
11 . The immunogenic composition of claim 10 , wherein the adjuvant is selected from the group consisting of cytokines, gel-type adjuvants, microbial adjuvants, oil-emulsion and emulsifier-based adjuvants, particulate adjuvants, synthetic adjuvants, polymer adjuvants, and/or combinations thereof.
12 . The immunogenic composition of claim 11 , wherein the particulate adjuvant is an aluminum salt.
13 . The immunogenic composition of claim 1 , wherein the VLP is produced by co-transfecting a host cell with a first vector comprising a nucleotide sequence of SEQ ID NO: 3 and a second vector comprising a nucleotide sequence of SEQ ID NO: 30; and
cultivating the host cell in a suitable medium under conditions allowing the expression of the proteins encoded by the vectors.
14 . A method of treating a subject having or at risk for coronavirus infection, comprising administering to the subject the pharmaceutical composition of claim 1 .
15 . The method of claim 14 wherein the pharmaceutical composition of claim 1 is administered as a booster following vaccination with a different vaccine against SARS-CoV-2.