Development of dengue virus vaccine components

Patent metadata

Field	Value
Publication number	US-10160957-B2
Application number	US-201514742533-A
Country	US
Kind code	B2
Filing date	Jun 17, 2015
Priority date	Aug 15, 2006
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The invention is related to a dengue virus or chimeric dengue virus that contains a mutation in the 3′ untranslated region (3′-UTR) comprising a Δ30 mutation that removes the TL-2 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, and nucleotides additional to the Δ30 mutation deleted from the 3′-UTR that removes sequence in the 5′ direction as far as the 5′ boundary of the TL-3 homologous structure in each of the dengue virus serotypes 1, 2, 3, and 4, or a replacement of the 3′-UTR of a dengue virus of a first serotype with the 3′-UTR of a dengue virus of a second serotype, optionally containing the Δ30 mutation and nucleotides additional to the Δ30 mutation deleted from the 3′-UTR; and immunogenic compositions, methods of inducing an immune response, and methods of producing a dengue virus or chimeric dengue virus.

First claim

What is claimed is:

1. A nucleic acid encoding a dengue virus or chimeric dengue virus comprising a mutation in the 3′ untranslated region (3′-UTR) comprising:
a Δ30 mutation that removes nucleotides 173 to 144 of dengue serotype 2 or nucleotides 172 to 143 of dengue serotype 4, using reverse-direction numbering, and nucleotides additional to the Δ30 mutation deleted from the 3′-UTR that removes sequence in the 5′ direction selected from the group consisting of:
nucleotides from about 228 to about 144 of DEN 2 or nucleotides from about 228 to about 143 of DEN4, designated with the reverse-direction numbering system; and
nucleotides from about 258 to about 228 of DEN 2 or nucleotides from about 258 to about 228 of DEN4, designated with the reverse-order numbering system.

2. An immunogenic composition comprising a nucleic acid encoding a dengue virus or chimeric dengue virus according to claim 1 or a dengue virus or chimeric dengue virus comprising said nucleic acid.

3. The immunogenic composition of claim 2 that is tetravalent for dengue serotypes 1, 2, 3, and 4.

4. A method of inducing an immune response to a dengue virus in a patient comprising administering the immunogenic composition of claim 2 to a patient to induce an immune response to a dengue virus.

5. A method of producing a nucleic acid encoding a dengue virus or chimeric dengue virus comprising introducing a mutation into the 3′ untranslated region (3′-UTR) comprising:
a Δ30 mutation that removes nucleotides 173 to 144 of dengue serotype 2 or nucleotides 172 to 143 of dengue serotype 4, using reverse-direction numbering, and nucleotides additional to the Δ30 mutation deleted from the 3′-UTR that removes sequence in the 5′ direction selected from the group consisting of:
nucleotides from about 228 to about 144 of DEN 2 or nucleotides from about 228 to about 143 of DEN4, designated with the reverse-direction numbering system; and
nucleotides from about 258 to about 228 of DEN 2 or nucleotides from about 258 to about 228 of DEN4, designated with the reverse-order numbering system.

6. A dengue virus or chimeric dengue virus comprising the nucleic acid encoding the dengue virus of claim 1 .

Assignees

• Us Health

Inventors

• Whitehead Stephen S
• Blaney Joseph E
• Murphy Brian R
• Lai Ching-Juh

Classifications

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C12N2770/24162

  by genetic engineering · CPC title

• C12N2770/24122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K2039/5254

  avirulent or attenuated · CPC title