MVA vaccine for delivery of a UL128 complex and preventing CMV infection
In one embodiment, an expression system for expressing a UL128 complex is provided herein. The expression system may include a bacterial artificial chromosome (BAC) construct, wherein the BAC construct comprises a viral vector inserted with a set of DNA sequences that encode a UL128 complex. In another embodiment, a vaccine composition for preventing HCMV infection is provided. The vaccine composition may include a viral or bacterial vector capable of expressing a UL128 complex and a pharmaceutically acceptable carrier, adjuvant, additive or combination thereof or additional vector expressing a protein adjuvant. The viral vector may be an MVA and the UL128 complex includes five HCMV proteins or antigenic fragments thereof: UL128, UL130, UL131A, gL, and gH. In some embodiments, the viral vector is further inserted with one or more additional DNA sequences that encode one or more additional HCMVHCMV proteins or antigenic fragments thereof such as pp65, gB or both, or such as gM/gN or gO.
1. An expression system comprising a bacterial artificial chromosome (BAC) construct, the BAC construct comprising a viral vector inserted with DNA sequences that encode cytomegalovirus (CMV) UL128, UL130, UL131A, glycoprotein L (gL), and glycoprotein H (gH) proteins or antigenic fragments thereof, wherein said proteins or fragments thereof form a UL128 complex, wherein the viral vector is derived from a poxvirus.
2. The expression system of claim 1 , wherein the viral vector is derived from an Avipoxvirus, an Orthopoxvirus, or a Parapoxvirus.
3. The expression system of claim 2 , wherein the Orthopoxvirus is a modified vaccinia Ankara (MVA) virus.
4. The expression system of claim 1 , wherein the viral vector is further inserted with one or more additional DNA sequences that encode one or more additional CMV proteins or antigenic fragments thereof selected from pp65, gB or both.
5. An immunogenic composition for inhibiting CMV infection comprising a viral vector capable of expressing CMV UL128, UL130, UL131A, gL, and gH proteins or antigenic fragments thereof, wherein said proteins or fragments thereof form a UL128 complex; and a pharmaceutically acceptable carrier, adjuvant, additive or combination thereof, wherein the viral vector is derived from a poxvirus.
6. The immunogenic composition of claim 5 , wherein the viral vector is derived from an Avipoxvirus, an Orthopoxvirus, or a Parapoxvirus.
7. The immunogenic composition of claim 6 , wherein the viral vector is a modified vaccinia Ankara (MVA) vector.
8. The immunogenic composition of claim 5 , wherein the viral vector is capable of expressing one or more additional CMV proteins or antigenic fragments thereof selected from pp65, glycoprotein B (gB) or both.
9. A method of inhibiting CMV entry into a cell comprising contacting the cell with an effective amount of the viral vector of claim 1 .
10. The method of claim 9 , wherein the viral vector is a poxvirus vector expressed from a bacterial artificial chromosome (BAC).
11. The method of claim 9 , wherein the viral vector is an MVA vector expressed from a bacterial artificial chromosome (BAC).
12. The method of claim 9 , wherein the vector further comprises one or more DNA sequences that encode additional CMV proteins or antigenic fragments thereof selected from pp65, gB, or both, or from gM/gN and gO.
13. The method of claim 9 , wherein the cell is an epithelial cell, an endothelial cell or a fibroblast.
14. A method for treating a CMV infection in a subject comprising administering a therapeutically effective amount of the immunogenic composition of claim 5 to said subject.
15. The method of claim 14 , wherein the viral vector is derived from an Avipoxvirus, an Orthopoxvirus, or a Parapoxvirus.
16. The method of claim 15 , wherein the viral vector is an MVA vector.
17. The method of claim 14 , wherein the viral vector further comprises one or more DNA sequences that encode additional CMV proteins or antigenic fragments thereof selected from pp65, gB or both.
18. The method of claim 14 , wherein the CMV infection is a congenital CMV infection.
19. The expression system of claim 1 , wherein each of the DNA sequences encoding a CMV protein are under the control of a promoter and a transcription termination sequence.
20. The expression system of claim 19 , wherein the promoter is a vaccinia virus mH5 promoter.