Adenovirus polynucleotides and polypeptides

Abstract

There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of:(a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1,(b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 80% identical over its entire length to the amino acid sequence of SEQ ID NO: 1, and(c) a polypeptide having the amino acid sequence according to SEQ ID NO: 3.

1 - 68 . (canceled) 
     
     
         69 . An isolated recombinant adenoviral polynucleotide encoding:
 (a) a polypeptide comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to the amino acid sequence set out in SEQ ID NO: 1;   (b) a polypeptide comprising an amino acid sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 99%, or 100% identical to the amino acid sequence set out in SEQ ID NO: 3;   (c) a polypeptide comprising an amino acid sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 99%, or 100% identical to the amino acid sequence set out in SEQ ID NO: 5; and   (d) an antigenic protein that is not isolated from or present in a naturally occurring adenovirus.   
     
     
         70 . The polynucleotide of  claim 69 , wherein the isolated recombinant adenoviral polynucleotide comprises a mutation or a deletion recombinantly introduced into the backbone of the adenoviral polynucleotide which renders non-function at least one gene of an adenoviral genomic region selected from the group consisting of E1A, E1B, E2A, E2B, E3, and E4. 
     
     
         71 . The polynucleotide of  claim 70 , wherein the genomic regions are E1A, E1B, or a combination thereof. 
     
     
         72 . The polynucleotide of  claim 69 , wherein the polynucleotide comprises at least one of the following:
 (a) an adenoviral 5′ inverted terminal repeat;   (b) an adenoviral E1A region, or a fragment thereof selected from the E1A_280R and E1A_243R regions;   (c) an adenoviral E1B or IX region, or a fragment thereof selected from the group consisting of the E1B_19K, E1B_55K, and IX regions;   (d) an adenoviral E2b region, or a fragment thereof selected from the group consisting of the E2B_pTP, E2B Polymerase and E2B_IVa2 regions;   (e) an adenoviral L1 region, or a fragment thereof, the fragment encoding an adenoviral protein selected from the group consisting of the L1_13.6k protein, L1_52k and L1_IIIa protein;   (f) an adenoviral L2 region, or a fragment thereof, the fragment encoding an adenoviral protein selected from the group consisting of the L2_penton protein, L2_pVII, L2_V, and L2_pX protein;   (g) an adenoviral L3 region, or a fragment thereof, the fragment encoding an adenoviral protein selected from the group consisting of the L3_pVI protein, L3_hexon protein and L3_protease;   (h) an adenoviral E2A region;   (i) an adenoviral L4 region, or a fragment thereof, the fragment encoding an adenoviral protein selected from the group consisting of the L4_100k protein, the L4_33k protein and protein L4_VIII;   (j) an adenoviral E3 region, or a fragment thereof, selected from the group consisting of E3 ORF1, E3 ORF2, E3 ORF3, E3 ORF4, E3 ORF5, E3 ORF6, E3 ORF7, E3 ORF5, and E3 ORF9;   (k) an adenoviral L5 region, or a fragment thereof, the fragment encoding the L5_fiber protein;   (l) an adenoviral E4 region, or a fragment thereof selected from the group consisting of E4 ORF7, E4 ORF6, E4 ORF4, E4 ORF3, E4 ORF2, and E4 ORF1;   (m) an adenoviral 3′ inverted terminal repeat; or   (n) an adenoviral VAI or VAII RNA region, wherein the VAI or VAII RNA region is from an adenovirus other than ChAd155.   
     
     
         73 . The polynucleotide according to  claim 69 , wherein the polynucleotide comprises a polynucleotide which is at least 98.6% identical to the polynucleotide sequence set out in SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. 
     
     
         74 . The polynucleotide according to  claim 69 , wherein the polynucleotide produces more viral particles per cell when infected into a host cell than a PanAd3 adenovirus encoding the same antigenic protein. 
     
     
         75 . A vector comprising the polynucleotide of  claim 69 . 
     
     
         76 . An isolated host cell comprising the polynucleotide of  claim 69 . 
     
     
         77 . A recombinant adenovirus comprising the polynucleotide of  claim 69 . 
     
     
         78 . The adenovirus of  claim 77 , wherein the recombinant adenovirus is replication-competent. 
     
     
         79 . The adenovirus of  claim 77 , wherein the recombinant adenovirus is replication-incompetent when infected into a host cell. 
     
     
         80 . The adenovirus of  claim 79 , wherein the adenovirus is rendered replication-incompetent by deletion in the E1A, E1B, or a combination thereof. 
     
     
         81 . The adenovirus of  claim 77 , wherein the adenovirus is capable of infecting a mammalian cell. 
     
     
         82 . The adenovirus of  claim 77 , wherein the adenovirus has a seroprevalence of less than 10% in human subjects. 
     
     
         83 . An immunogenic composition comprising the polynucleotide of  claim 69 . 
     
     
         84 . An immunogenic composition comprising the adenovirus of  claim 77 . 
     
     
         85 . The immunogenic composition of  claim 83 , further comprising an adjuvant, wherein the adjuvant is selected from the group consisting of inorganic adjuvants, organic adjuvants, oil-based adjuvants, cytokines particulate adjuvants, liposomes, biodegradable microspheres, virosomes, bacterial adjuvants, synthetic adjuvants, synthetic polynucleotides adjuvants, and immunostimulatory oligonucleotides containing unmethylated CpG dinucleotides (“CpG”). 
     
     
         86 . The immunogenic composition of  claim 83 , further comprising a pharmaceutically acceptable excipient. 
     
     
         87 . A vaccine composition comprising the immunogenic composition of  claim 83 . 
     
     
         88 . A method of inducing an immune response in a subject comprising administering to the subject an immunogenic composition comprising an isolated recombinant adenoviral polynucleotide encoding:
 (a) a polypeptide comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to the amino acid sequence set out in SEQ ID NO: 1;   (b) a polypeptide comprising an amino acid sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 99%, or 100% identical to the amino acid sequence set out in SEQ ID NO: 3;   (c) a polypeptide comprising an amino acid sequence that is at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 99%, or 100% identical to the amino acid sequence set out in SEQ ID NO: 5; and   (d) an antigenic protein that is not isolated from or present in a naturally occurring adenovirus.   
     
     
         89 . The method of  claim 88 , wherein the immunogenic composition further comprises a pharmaceutically acceptable excipient, an adjuvant, or a combination thereof.