Synthetic human papilloma virus genes
View Patent ↗Synthetic DNA molecules encoding papillomavirus proteins are provided. The codons of the synthetic molecules are codons preferred by the projected host cell. The synthetic molecules may be used as a polynucleotide vaccine which provides effective immunoprophylaxis against papillomavirus infection through stimulation of neutralizing antibody and cell-mediated immunity.
1. A method for inducing immune responses to HPV16 in a human subject which comprises administering to the subject a composition comprising between 1 ng and 100 mg of a plasmid vaccine vector and a pharmaceutically acceptable carrier, said plasmid vaccine vector comprising a synthetic polynucleotide, the synthetic polynucleotide comprising a sequence encoding a codon-optimized human papillomavirus serotype 16 (HPV16) protein, wherein said polynucleotide sequence comprises codons that are optimized for high-level expression in a human host.
2. A method for inducing immune responses to HPV16 in a human subject which comprises administering to the subject between 10 11 –10 12 particles of an adenoviral vector carrying a synthetic polynucleotide, the synthetic polynucleotide comprising a sequence encoding a codon-optimized human papillomavirus serotype 16 (HPV 16) protein, wherein said polynucleotide sequence comprises codons that are optimized for high-level expression in a human host.
3. A method for inducing an immune response against human papillomavirus type 16 (HPV16) in a human subject, comprising
a) administering to the subject a first vector comprising a polynucleotide encoding a codon-optimized HPV16 protein selected from the group consisting of L1, E1, E2, and E7 proteins, wherein said polynucleotide is codon-optimized for expression in a human host cell;
b) allowing a predetermined amount of time to pass; and
c) administering to said subject a second vector comprising adenoviral vaccine vector comprising an adenoviral genome with a deletion in the E1 region, and an insert in the E1 region, wherein the insert comprises an expression cassette comprises
i) a polynucleotide encoding a codon-optimized HPV 16 protein selected from the group consisting of L1, E1, E2, and E7 proteins, wherein said polynucleotide is codon-optimized for expression in a human host cell; and
ii) a promoter operably linked to the polynucleotide.
4. A method for inducing immune responses to HPV16 in a human subject comprising
a) administering to the subject a plasmid vaccine, wherein the plasmid vaccine comprises a plasmid portion and an expression cassette portion, the expression cassette portion comprising:
i) a polynucleotide encoding a codon-optimized HPV16 protein selected from the group consisting of L1, E1, E2, and E7 proteins, wherein said polynucleotide is codon-optimized for expression in a human host cell; and
ii) a promoter operably linked to the polynucleotide;
b) allowing a predetermined amount of time to pass; and
c) administering to said subject an adenoviral vaccine vector comprising an adenoviral genome with a deletion in the E1 region, and an insert in the E1 region, wherein the insert comprises an expression cassette comprising:
i) a polynucleotide encoding a codon-optimized HPV16 protein selected from the group consisting of L1, E1, E2, and E7 proteins, wherein said polynucleotide is codon-optimized for expression in a human host cell; and
ii) a promoter operably linked to the polynucleotide.