Vaccinia viral vectors encoding chimeric virus like particles
AssigneeGeoVax, Inc.
InventorsHarriet Robinson, Arban Domi, Michael Hellerstein, Farshad Guirakhoo, Nathanael Paul McCurley
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Abstract
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.
Claims21
A method of inducing an immunological response in a human to a tumor associated antigen (TAA), the method comprising administering to the human a pharmaceutical composition comprising a recombinant modified vaccinia Ankara (MVA) viral vector in an amount sufficient to induce an immune response to the TAA, wherein the recombinant MVA viral vector comprises:
- (i) a first nucleic acid sequence encoding a chimeric protein comprising (a) an extracellular fragment of the TAA, (b) a transmembrane domain of a glycoprotein (GP) of Marburg virus, and (c) an intracellular fragment of the TAA;
- and
- (ii) a second nucleic acid sequence encoding a Marburg virus VP40 matrix protein;
- wherein both the first nucleic acid sequence and the second 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).
A method of inducing an immunological response in a human to mucin-1 (MUC-1), the method comprising administering a pharmaceutical composition comprising a recombinant modified vaccinia Ankara (MVA) viral vector to the human in an amount sufficient to induce an immune response to MUC-1, wherein the recombinant MVA viral vector comprises:
- (i) a first nucleic acid sequence encoding a chimeric protein comprising (a) a MUC-1 antigenic peptide and (b) a transmembrane domain of a viral glycoprotein (GP) of Marburg virus, wherein the first nucleic acid sequence encodes an amino acid sequence comprising the amino acid sequence of SEQ ID NO:
- 15, or an amino acid sequence at least 95% identical thereto, and
- (ii) a second nucleic acid sequence encoding a viral Marburg virus VP40 matrix protein;
- wherein the first nucleic acid sequence and second 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).
A method of inducing an immunological response in a human to MUC-1, the method comprising administering a pharmaceutical composition comprising a recombinant modified vaccinia Ankara (MVA) viral vector to the human in an amount sufficient to induce an immune response, wherein the recombinant MVA viral vector comprises:
- (i) a first nucleic acid sequence comprising the nucleic acid sequence of SEQ ID NO:
- 29, or a nucleic acid sequence at least 95% identical thereto, encoding a chimeric protein comprising the amino acid sequence of SEQ ID NO:
- 15, or an amino acid sequence at least 95% identical thereto, and
- (ii) a second nucleic acid sequence encoding a Marburg virus VP40 matrix protein;
- wherein the first nucleic acid sequence and second nucleic acid sequence are under the control of a PmH5 promoter;
- wherein the first nucleic acid sequence is inserted between essential MVA genes 18R and G1L;
- wherein the second nucleic acid sequence is inserted in restructured and modified MVA deletion III region between MVA genes A50R and BIR;
- and,
- wherein upon expression, the chimeric protein and VP40 matrix protein are capable of assembling together to form virus-like particles (VLPs).
Dependencies are inferred from the claim text.