Vaccinia viral vectors encoding chimeric virus like particles
The compositions and methods are described for generating an immune response to an antigen. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens as a fusion product with a viral glycoprotein and matrix protein for generating a protective immune response to a subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat diseases.
1. A recombinant modified vaccinia Ankara (MVA) viral vector comprising:
(i) a first heterologous nucleic acid sequence encoding a chimeric protein comprising (a) a mucin-1 (MUC-1) antigenic peptide and (b) a transmembrane domain of a viral glycoprotein (GP) of Marburg virus, wherein the first heterologous nucleic acid sequence encodes an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 15, or an amino acid sequence 98% identical thereto, and
(ii) a second heterologous nucleic acid sequence encoding a viral Marburg virus VP40 matrix protein;
wherein the first heterologous nucleic acid sequence and second heterologous nucleic acid sequence are under the control of one or more promoters compatible with poxvirus expression systems, and wherein upon expression, the chimeric protein and VP40 matrix protein are capable of assembling together to form virus like particles (VLPs).
2. The recombinant MVA viral vector of claim 1 , wherein the promoter is selected from the group consisting of Pm2H5, Psyn II, and PmH5, or combinations thereof.
3. The recombinant MVA viral vector of claim 1 , wherein the first heterologous nucleic acid sequence-encodes an amino acid sequence comprising the amino acid sequence of SEQ ID NO:15.
4. The recombinant MVA viral vector of claim 2 , wherein the first heterologous nucleic acid sequence is under the control of the PmH5 promoter.
5. The recombinant MVA viral vector of claim 2 , wherein the second heterologous nucleic acid sequence is under the control of the PmH5 promoter.
6. The recombinant MVA of claim 1 , wherein the first heterologous nucleic acid sequence is inserted between essential genes of MVA I8R and G1L.
7. The recombinant MVA of claim 1 , wherein the second heterologous nucleic acid sequence is inserted in restructured and modified MVA deletion III region between MVA genes A50R and B1R.
8. The recombinant MVA viral vector of claim 1 , wherein the first heterologous nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 16, or a nucleic acid sequence at least 95% identical thereto.
9. The recombinant MVA viral vector of claim 8 , wherein the first heterologous nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 16.
10. The recombinant MVA viral vector of claim 1 , wherein the first heterologous nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 18, or a nucleic acid sequence at least 95% identical thereto.
11. The recombinant MVA viral vector of claim 10 , wherein the first heterologous nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 18.
12. The recombinant MVA viral vector of claim 1 , wherein the first heterologous nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 29, or a nucleic acid sequence at least 95% identical thereto.
13. The recombinant MVA viral vector of claim 12 , wherein the first heterologous nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 29.
14. A recombinant MVA viral vector comprising:
(i) a first heterologous nucleic acid sequence comprising the nucleic acid sequence of SEQ ID NO:29 encoding a chimeric protein comprising the amino acid sequence of SEQ ID NO: 15, and
(ii) a second heterologous nucleic acid sequence encoding a viral Marburg virus VP40 matrix protein;
wherein the first heterologous nucleic acid sequence and second heterologous nucleic acid sequence are under the control of a PmH5 promoter;
wherein the first heterologous nucleic acid sequence is inserted between essential genes of MVA I8R and G1L;
wherein the second heterologous nucleic acid sequence is inserted in restructured and modified MVA deletion III region between MVA genes A50R and B1R; and,
wherein upon expression, the chimeric protein and VP40 matrix protein are capable of assembling together to form VLPs.