Vaccine compositions of herpesvirus envelope protein combinations to induce immune response

Abstract

Provided are antigenic compositions and uses thereof that include at least two human herpesvirus (HHV) polypeptides involved in mediating HHV binding, fusion, and entry into host cells, such as gp350, gH, gL, and gB, or nucleic acids encoding the polypeptides. The two HHV polypeptides comprise any combination of: a gB polypeptide; a gp350 polypeptide; a gL polypeptide; and a gH polypeptide, and optionally any one or more of the following polypeptides: gp42, gM, gN, gl, gC, gE, gD, ORF68, BMRF-2, BDLF2, UL128, UL130, UL131A, and gpK8.1. Also disclosed are methods of inducing an immune response or treating or preventing an HHV infection in a subject by administering to the subject at least two of the HHV polypeptides or nucleic acid(s) encoding the same. Methods of passively transferring immunity using high-titer anti-HHV antibodies or immune cells are also disclosed.

1 . An antigenic composition comprising at least two human herpesvirus polypeptides or one or more nucleic acids encoding the at least two human herpesvirus polypeptides, wherein the antigenic composition comprises at least a first human herpesvirus polypeptide and at least a second human herpesvirus polypeptide,
 wherein the first human herpesvirus polypeptide comprises   a monomeric or multimeric glycoprotein B (gB) polypeptide comprising an extracellular domain of human herpesvirus gB; and   the second human herpesvirus polypeptide comprises a monomeric or multimeric glycoprotein gH/glycoprotein gL (gH/gL) heterodimer comprising a gL polypeptide and   a gH polypeptide comprising an extracellular domain of human herpesvirus gH.   
     
     
         2 . The composition of  claim 1 , wherein the human herpes virus is human cytomegalovirus (HCMV), Herpes Simplex Virus-1 (HSV-1), Herpes Simplex Virus-2 (HSV-2), Varicella-Zoster Virus (VZV), Epstein-Barr Virus (EBV), Human Herpes Virus 6 (HHV-6), Human Herpes Virus 7 (HHV-7), or Kaposi Sarcoma-related Herpes Virus (KSHV). 
     
     
         3 . The composition of  claim 1 , wherein the gB polypeptide and/or the gH polypeptide each further comprises a corresponding gB and/or gH intracellular domain, respectively. 
     
     
         4 . The composition of  claim 3 , wherein the extracellular domain is fused to the intracellular domain via a polypeptide linker sequence. 
     
     
         5 . The composition of  claim 4 , wherein the polypeptide linker sequence is about 6 to about 70 amino acids in length, or wherein the peptide linker is about 15 amino acids in length. 
     
     
         6 . The composition of  claim 1  wherein the first herpesvirus protein does not form a fusion protein with the second human herpesvirus protein. 
     
     
         7 . (canceled) 
     
     
         8 . The composition of  claim 1 , wherein the gB polypeptide is multimeric. 
     
     
         9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein the gB polypeptide is monomeric, dimeric or trimeric and the gH/gL heterodimer is monomeric. 
     
     
         11 . The composition of  claim 1 , wherein the at least two human herpesvirus polypeptides are HCMV polypeptides. 
     
     
         12 . The composition of  claim 11 , wherein the composition further comprises an HCMV glycoprotein O (gO) polypeptide. 
     
     
         13 . The composition of  claim 11 , wherein the composition further comprises an HCMV unique long 128 (UL128) polypeptide, an HCMV unique long 130 (UL130) polypeptide, an HCMV unique long 131A (UL131A) polypeptide, and optionally an HCMV glycoprotein M (gM) polypeptide, and/or an HCMV glycoprotein N (gN) polypeptide. 
     
     
         14 . The composition of  claim 1 , wherein the at least two human herpesvirus polypeptides are human EBV polypeptides. 
     
     
         15 .- 19 . (canceled) 
     
     
         20 . The composition of  claim 14 , wherein the gB polypeptide is trimeric gB, and wherein the gH polypeptide and gL polypeptide form a monomeric or trimeric gH/gL heterodimer. 
     
     
         21 .- 22 . (canceled) 
     
     
         23 . The composition of  claim 20 , further comprising a human EBV glycoprotein 42 (gp42) polypeptide, BDFL2 polypeptide, and/or a human EBV BMRF-2 polypeptide. 
     
     
         24 . The composition of  claim 1 , wherein the at least two human herpesvirus polypeptides are human HSV-1 or HSV-2 polypeptides. 
     
     
         25 . The composition of  claim 24 , wherein the gB polypeptide is monomeric, dimeric, or trimeric, and optionally wherein the at least two human herpesvirus polypeptides comprise a monomeric gH/gL heterodimer formed by the gH polypeptide and the gL polypeptide and a monomeric gB polypeptide. 
     
     
         26 . The composition of  claim 25 , further comprising an HSV-1 or HSV-2 glycoprotein D (gD) polypeptide, wherein the gD polypeptide is monomeric, dimeric, trimeric, or tetrameric. 
     
     
         27 . The composition of  claim 1 , wherein the at least two human herpesvirus polypeptides are human VZV polypeptides. 
     
     
         28 . The composition of  claim 27 , wherein the gB polypeptide is monomeric, dimeric, or trimeric, and optionally wherein the at least two human herpesvirus polypeptides comprise a monomeric gH/gL heterodimer formed by the gH polypeptide and the gL polypeptide and a monomeric gB polypeptide. 
     
     
         29 . The composition of  claim 28 , further comprising one or more of a human VZV glycoprotein C (gC) polypeptide, human glycoprotein E (gE) polypeptide, and human VZV glycoprotein I (gI) polypeptide. 
     
     
         30 . The composition of  claim 1 , wherein the at least two human herpesvirus polypeptides are human HHV-6 or HHV-7 polypeptides. 
     
     
         31 . The composition of  claim 30 , wherein wherein the gB polypeptide is monomeric, dimeric, or trimeric, and optionally wherein the at least two human herpesvirus polypeptides comprise a monomeric gH/gL heterodimer formed by the gH polypeptide and the gL polypeptide and a monomeric gB polypeptide. 
     
     
         32 . The composition of  claim 1 , wherein the at least two human herpesvirus polypeptides are human KSHV polypeptides. 
     
     
         33 . The composition of  claim 32 , wherein the gB polypeptide is monomeric, dimeric, or trimeric, and optionally wherein the at least two human herpesvirus polypeptides comprise a monomeric gH/gL heterodimer formed by the gH polypeptide and the gL polypeptide and a monomeric gB polypeptide. 
     
     
         34 . The composition of  claim 33 , further comprising one or more of a human KSHV glycoprotein M (gM) polypeptide, a human KSHV glycoprotein N (gN) polypeptide, a human KSHV Open Reading Frame 68 (ORF68) polypeptide, and a human KSHV glycoprotein K8.1 polypeptide. 
     
     
         35 . The composition of  claim 1 , wherein the one or more nucleic acids are in a viral vector that permits expression of the at least two human herpesvirus polypeptides. 
     
     
         36 . The composition of  claim 1 , further comprising a pharmaceutically acceptable excipient and/or an adjuvant. 
     
     
         37 . A method for preventing or treating a human herpesvirus infection in a subject comprising administering to the subject a therapeutically effective amount of the composition of  claim 1 . 
     
     
         38 . A method for inducing immunity to a human herpesvirus in a subject comprising administering to the subject a therapeutically effective amount of the composition of  claim 1 . 
     
     
         39 . The method of  claim 37 , wherein the subject is at risk of developing post-transplantation lymphoproliferative disorder (PTLD) following hematopoietic stem cell or solid organ transplantation and suffers from a primary immunodeficiency syndrome. 
     
     
         40 . The method of  claim 37 , wherein the at least two human herpesvirus polypeptides in the composition are administered sequentially or concurrently. 
     
     
         41 .- 93 . (canceled)