Dengue tetravalent vaccine containing a common 30 nucleotide deletion in the 3′-UTR of dengue types 1,2,3, and 4, or antigenic chimeric dengue viruses 1,2,3, and 4

Patent metadata

Field	Value
Publication number	US-RE46641-E
Application number	US-201313896388-A
Country	US
Kind code	E1
Filing date	May 17, 2013
Priority date	May 3, 2002
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

The invention relates to a dengue virus tetravalent vaccine containing a common 30 nucleotide deletion (Δ30) in the 3′-untranslated region of the genome of dengue virus serotypes 1, 2, 3, and 4, or antigenic chimeric dengue viruses of serotypes 1, 2, 3, and 4.

First claim

What is claimed is:

1. A tetravalent immunogenic composition comprising
a) a first attenuated virus that is immunogenic against dengue serotype 1 comprising a nucleic acid that encodes at least one structural protein from dengue serotype 1 and nonstructural proteins from dengue serotype 1 or dengue serotype 4;
b) a second attenuated virus that is immunogenic against dengue serotype 2 comprising a nucleic acid that encodes at least one structural protein from dengue serotype 2 and nonstructural proteins from dengue serotype 4;
c) a third attenuated virus that is immunogenic against dengue serotype 3 comprising a nucleic acid that encodes at least one structural protein from dengue serotype 3 and nonstructural proteins from dengue serotype 3 or dengue serotype 4; and
d) a fourth attenuated virus that is immunogenic against dengue serotype 4 comprising a nucleic acid that encodes at least one structural protein from dengue serotype 4 and nonstructural proteins from dengue serotype 4,
wherein the first attenuated virus, the second attenuated virus, the third attenuated virus, and the fourth attenuated virus each comprise a 3′ untranslated region, and
wherein the 3′ untranslated region contains a deletion of about 30 nucleotides corresponding to the TL2 stem-loop structure of dengue serotype 1, dengue serotype 3, or dengue serotype 4;
wherein the tetravalent immunogenic composition is not a combination of rDEN1/4Δ30, rDEN2/4Δ30, rDEN3/4Δ30, and rDEN4Δ30.

2. The tetravalent immunogenic composition of claim 1 , wherein the nucleic acid of at least one of a), b), c) or d) further comprises a mutation that confers a phenotype wherein the phenotype is host-cell adaptation for improved replication in Vero cells, or attenuation in mice or monkeys.

3. The composition of claim 1 , wherein the 3′ untranslated region of a) comprises a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 1 genome corresponding to the TL2 stem-loop structure between about nucleotides 10562-10591.

4. The composition of claim 1 , wherein the 3′ untranslated region of a) comprises a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507.

5. The composition of claim 1 , wherein the 3′ untranslated region of b) comprises a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507.

6. The composition of claim 1 , wherein the 3′ untranslated region of c) comprises a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507.

7. The composition of claim 1 , wherein the 3′ untranslated region of d) comprises a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507.

8. The composition of claim 1 , wherein the nucleic acid that encodes at least one structural protein from dengue serotype 1 encodes at least two structural proteins from dengue serotype 1.

9. The composition of claim 1 , wherein the nucleic acid that encodes at least one structural protein from dengue serotype 2 encodes at least two structural proteins from dengue serotype 2.

10. The composition of claim 1 , wherein the nucleic acid that encodes at least one structural protein from dengue serotype 3 encodes at least two structural proteins from dengue serotype 3.

11. The composition of claim 1 , wherein the nucleic acid that encodes at least one structural protein from dengue serotype 4 encodes at least two structural proteins from dengue serotype 4.

12. The composition of claim 8 , wherein the at least two structural proteins from dengue serotype 1 are prM and E proteins.

13. The composition of claim 8 , wherein the at least two structural proteins from dengue serotype 1 are C, prM and E proteins.

14. The composition of claim 9 , wherein the at least two structural proteins from dengue serotype 2 are prM and E proteins.

15. The composition of claim 10 , wherein the at least two structural proteins from dengue serotype 3 are C, prM and E proteins.

16. The composition of claim 11 , wherein the at least two structural proteins from dengue serotype 4 are C, prM and E proteins.

17. The composition of claim 12 ,
wherein the at least one structural protein from dengue serotype 2 is prM and E proteins;
wherein the at least one structural protein from dengue serotype 3 is C, prM and E proteins;
wherein the at least one structural protein from dengue serotype 4 is C, prM and E proteins;
wherein the deletion of a) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507;
wherein the deletion of b) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507;
wherein the deletion of c) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507;
wherein the deletion of d) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507.

18. The composition of claim 13 ,
wherein the at least one structural protein from dengue serotype 2 is prM and E proteins,
wherein the at least one structural protein from dengue serotype 3 is C, prM and E proteins;
wherein the at least one structural protein from dengue serotype 4 is C, prM and E proteins;
wherein the deletion of a) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 1 genome corresponding to the TL2 stem-loop structure between about nucleotides 10562-10591;
wherein the deletion of b) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507;
wherein the deletion of c) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507;
wherein the deletion of d) is a deletion of about 30 nucleotides from the 3′ untranslated region of the dengue type 4 genome corresponding to the TL2 stem-loop structure between about nucleotides 10478-10507.

19. The composition of claim 1 which is a combination of rDEN1/4Δ30, rDEN2/4Δ30, rDEN3Δ30, and rDEN4Δ30.

20. The composition of claim 1 which is a combination of rDEN1/4Δ30, rDEN2/4Δ30, rDEN1/3Δ30, rDEN2/3Δ30, rDEN3Δ30, and rDEN4Δ30.

21. The composition of claim 1 which is a combination of rDEN1/4Δ30, rDEN2/4Δ30, rDEN3Δ30, and rDEN4Δ30.

22. A method of inducing an immune response in a subject comprising administering an effective amount of the composition of claim 1 to the subject.

23. The method of claim 22 wherein the subject is a human.

24. A method of inducing an immune response in a subject comprising administering an effective amount of the composition of claim 17 to th

Assignees

• The Us Secretary Department Of Health & Human Services
• Us Health

Inventors

• Whitehead Stephen S
• Murphy Brian R
• Markoff Lewis
• Falgout Barry
• Blaney Joseph E
• Hanley Kathryn A
• Lai Ching-Juh

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61K39/12

  Viral antigens · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/5254

  avirulent or attenuated · CPC title