Complexes of cytomegalovirus proteins

Abstract

An isolated human cytomegalovirus (HCMV) membrane protein complex that comprises gH, gL and at least one more HCMV glycoprotein is provided. In some embodiments the complex consists of gH, gL and gO. In other embodiments the complex consists of gH, gL, pUL128, pUL130 and pUL131A. Processes for expressing and purifying such complexes, and subsequent uses of such complexes in immunogenic compositions and vaccines, are also provided.

1 - 27 . (canceled) 
     
     
         28 . A method of treating HCMV infection, comprising administering to a subject in need thereof an immunologically effective amount of a composition comprising a human Cytomegalovirus (HCMV) pentameric complex,
 wherein the HCMV pentameric complex comprises
 a pentamer-forming fragment of HCMV gH having a truncated transmembrane (TM) domain and a truncated ectodomain as compared to wild-type HCMV gH; 
 HCMV gL or pentamer-forming fragment thereof; 
 HCMV pUL128 or pentamer-forming fragment thereof; 
 HCMV pUL130 or pentamer-forming fragment thereof; and 
 HCMV pUL131A or pentamer-forming fragment thereof, 
   wherein the truncated TM domain consists of an amino acid sequence having a deletion of the amino acids corresponding to residues 718 to 736 of wild-type sequence SEQ ID NO: 1, and wherein the truncated ectodomain consists of an amino acid sequence having a deletion of the amino acids corresponding to residues 716 and 717 of wild-type sequence SEQ ID NO: 1.   
     
     
         29 . The method of  claim 28 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 7-9 and 31. 
     
     
         30 . The method of  claim 28 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 7-9 and 31. 
     
     
         31 . The method of  claim 28 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 7-9 and 31. 
     
     
         32 . The method of  claim 28 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 7-9 and 31. 
     
     
         33 . The method of  claim 28 , wherein said gL, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 7-9 and 31. 
     
     
         34 . The method of  claim 28 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 13-15 and 33. 
     
     
         35 . The method of  claim 28 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 13-15 and 33. 
     
     
         36 . The method of  claim 28 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 13-15 and 33. 
     
     
         37 . The method of  claim 28 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 13-15 and 33. 
     
     
         38 . The method of  claim 28 , wherein said pUL128, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 13-15 and 33. 
     
     
         39 . The method of  claim 28 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 16, 17, and 34. 
     
     
         40 . The method of  claim 28 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 16, 17, and 34. 
     
     
         41 . The method of  claim 28 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 16, 17, and 34. 
     
     
         42 . The method of  claim 28 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 16, 17, and 34. 
     
     
         43 . The method of  claim 28 , wherein said pUL130, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 16, 17, and 34. 
     
     
         44 . The method of  claim 28 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 18-20, and 35. 
     
     
         45 . The method of  claim 28 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 18-20, and 35. 
     
     
         46 . The method of  claim 28 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 18-20, and 35. 
     
     
         47 . The method of  claim 28 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 18-20, and 35. 
     
     
         48 . The method of  claim 28 , wherein said pUL131A, or pentamer-forming fragment thereof, comprises a sequence selected from the group consisting of SEQ ID NOs: 18-20, and 35. 
     
     
         49 . The method of  claim 28 , wherein the composition is a pharmaceutical composition comprising the purified HCMV pentameric complex and an adjuvant. 
     
     
         50 . The method of  claim 49 , wherein the adjuvant comprises an aluminum salt, an oil-in-water emulsion, or a combination thereof. 
     
     
         51 . The method of  claim 50 , wherein the adjuvant comprising an aluminum salt comprises aluminum hydroxide, aluminum oxyhydroxide, aluminum hydroxide adsorbed to a TLR7 agonist, or a combination thereof. 
     
     
         52 . The method of  claim 50 , wherein the oil-in-water emulsion comprises MF59, AS03, or a combination thereof. 
     
     
         53 . The method of  claim 28 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 80% identical to any one of SEQ ID NOs: 4, 6, 29, and 30. 
     
     
         54 . The method of  claim 28 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 85% identical to any one of SEQ ID NOs: 4, 6, 29, and 30. 
     
     
         55 . The method of  claim 28 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 90% identical to any one of SEQ ID NOs: 4, 6, 29, and 30. 
     
     
         56 . The method of  claim 28 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence that is at least 95% identical to any one of SEQ ID NOs: 4, 6, 29, and 30. 
     
     
         57 . The method of  claim 28 , wherein said pentamer-forming fragment of HCMV gH comprises a sequence selected from the group consisting of SEQ ID NOs: 4, 6, 29, and 30. 
     
     
         58 . The method of  claim 57 , wherein said pentamer-forming fragment of HCMV gH comprises the sequence SEQ ID NO: 6.