Human cytomegalovirus vaccine

Abstract

The disclosure relates to HCMV ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

1 .- 180 . (canceled) 
     
     
         181 . A human cytomegalovirus (HCMV) vaccine comprising:
 an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide pp65, or an antigenic fragment or epitope thereof, and a pharmaceutically acceptable carrier or excipient, wherein the RNA polynucleotide is formulated in at least one lipid nanoparticle comprising 20-60 mole percent ionizable cationic lipid of Compound 25:   
       
         
           
           
               
               
           
         
       
       0.5-15 mole percent PEG-modified lipid, 25-55 mole percent sterol, and 5-25 mole percent non-cationic lipid that is not a sterol. 
     
     
         182 . The HCMV vaccine of  claim 181 , wherein the pp65 polypeptide contains a deletion of amino acids 435-438. 
     
     
         183 . The HCMV vaccine of  claim 181 , wherein the RNA polynucleotide in the HCMV vaccine is a messenger ribonucleotide polynucleotides (mRNA), and wherein the mRNA polynucleotide contains a 5′ terminal CAP structure, a 5′ untranslated region (UTR), an open reading frame (ORF), a 3′ untranslated region (UTR) and a 3′ terminal poly-A tail. 
     
     
         184 . The HCMV vaccine of  claim 181 , wherein the HCMV vaccine further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         185 . The HCMV vaccine of  claim 181 , wherein the RNA polynucleotide further comprises a 5′ terminal cap, 7mG(5′)ppp(5′)NlmpNp. 
     
     
         186 . The HCMV vaccine of  claim 181 , wherein at least 80% of the uracil in the open reading frame have a chemical modification selected from 1-methyl-pseudouridine or 1-ethyl-pseudouridine. 
     
     
         187 . The HCMV vaccine of  claim 181 , wherein the chemical modification is in the carbon-5 position of the uracil. 
     
     
         188 . The HCMV vaccine of  claim 181 , wherein the RNA polynucleotide is not self-replicating RNA. 
     
     
         189 . A kit comprising:
 (i) a first HCMV vaccine comprising an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide pp65, or an antigenic fragment or epitope thereof, and   (ii) a second HCMV vaccine comprising at least one RNA polynucleotide having one or more open reading frames encoding HCMV antigenic polypeptides gH, gL, UL128, UL130, and/or UL131A, or antigenic fragments or epitopes thereof; and an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gB, or an antigenic fragment or epitope thereof.   
     
     
         190 . The kit of  claim 189 , wherein the first HCMV vaccine is administered at least 1 week, at least 2 weeks, or at least 3 weeks prior to administering the second HCMV vaccine. 
     
     
         191 . The kit of  claim 189 , wherein the pp65 polypeptide contains a deletion of amino acids 435-438. 
     
     
         192 . The kit of  claim 189 , wherein the second HCMV vaccine comprises: an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gH, or an antigenic fragment or epitope thereof; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gL, or an antigenic fragment or epitope thereof; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide UL128, or an antigenic fragment or epitope thereof; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide UL130, or an antigenic fragment or epitope thereof; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide UL131A, or an antigenic fragment or epitope thereof; an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide gB, or an antigenic fragment or epitope thereof; and an RNA polynucleotide having an open reading frame encoding HCMV antigenic polypeptide pp65, or an antigenic fragment or epitope thereof. 
     
     
         193 . The kit of  claim 189 , wherein one or more of the RNA polynucleotides in the first and or second HCMV vaccine are codon optimized. 
     
     
         194 . The kit of  claim 189 , wherein at least one of the RNA polynucleotides encodes an antigenic polypeptide having at least 90% identity to any of the amino acid sequences of SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 67, SEQ ID NO: 69, SEQ ID NO: 71, SEQ ID NO: 73, SEQ ID NO: 77, and SEQ ID NOs: 80-83. 
     
     
         195 . The kit of  claim 189 , wherein the first and/or second HCMV vaccine is formulated within a cationic lipid nanoparticle. 
     
     
         196 . The kit of  claim 195 , wherein the lipid nanoparticle(s) comprise a molar ratio of 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid. 
     
     
         197 . The kit of  claim 189 , wherein the first and/or second HCMV vaccine further comprises a pharmaceutically acceptable carrier or excipient. 
     
     
         198 . The kit of  claim 189 , wherein at least one RNA polynucleotide further encodes at least one 5′ terminal cap, 7mG(5′)ppp(5′)NlmpNp. 
     
     
         199 . The kit of  claim 189 , for use in preventing or treating HCMV infection in a subject. 
     
     
         200 . The kit of  claim 199 , wherein the subject is an immunocompromised organ transplant recipient.