Compositions and methods for generating an immune response to hepatitis B virus
The compositions and methods are described for generating an immune response to a hepatitis B virus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a hepatitis B virus, in the 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 an infection caused by hepatitis B virus.
1. A modified vaccinia Ankara (MVA) vector comprising a first nucleic acid sequence and a second nucleic acid sequence, wherein:
the first nucleic acid sequence encodes a hepatitis B virus structural fusion protein comprising a fragment of the PreS-S protein lacking all or part of the S domain and fused to the N-terminus of an influenza virus hemagglutinin A (HA) protein transmembrane domain, and wherein the first nucleic acid sequence is inserted into the MVA vector under the control of at least one promoter compatible with a poxvirus expression system;
the second nucleic acid sequence encodes influenza virus M1.P41A matrix protein, and wherein the second nucleic acid sequence is inserted into the MVA vector under the control of at least one promoter compatible with a poxvirus expression system; and,
the hepatitis B virus structural fusion protein and influenza virus M1.P41A matrix protein assemble into virus-like particles (VLPs) when expressed.
2. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the first nucleic acid sequence is inserted between MVA genes I8R and G1L.
3. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the first nucleic acid sequence is inserted between MVA genes I8R and G1L, and the second nucleic acid sequence is inserted in modified deletion III.
4. A pharmaceutical composition comprising the modified vaccinia Ankara (MVA) vector of claim 1 , and a pharmaceutically acceptable carrier.
5. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the promoter is selected from the group consisting of Pm2H5, Psyn II, mH5 promoters and combinations thereof.
6. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the first nucleic acid sequence comprises SEQ ID NO: 4.
7. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the first nucleic acid sequence encodes the amino acid sequence comprising SEQ ID NO: 7.
8. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the second nucleic acid sequence comprises SEQ ID NO: 5.
9. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the second nucleic acid sequence encodes the amino acid sequence comprising SEQ ID NO: 8.
10. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the first nucleic acid sequence comprises SEQ ID NO: 4 and the second nucleic acid sequence comprises SEQ ID NO: 5.
11. The modified vaccinia Ankara (MVA) vector of claim 1 , wherein the first nucleic acid sequence encodes the amino acid sequence comprising SEQ ID NO: 7, and the second nucleic acid sequence encodes the amino acid sequence comprising SEQ ID NO: 8.