P
USRE46641EExpiredUtilityPatentIndex 83

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

Assignee: THE US SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICESPriority: May 3, 2002Filed: May 17, 2013Granted: Dec 19, 2017
Est. expiryMay 3, 2022(expired)· nominal 20-yr term from priority
Inventors:WHITEHEAD STEPHEN SMURPHY BRIAN RMARKOFF LEWISFALGOUT BARRYBLANEY JOSEPH EHANLEY KATHRYN ALAI CHING-JUH
A61P 37/04A61P 31/14A61K 39/12A61K 2039/70A61K 2039/5254C12N 2770/24161C12N 7/00C12N 2770/24134A61K 2039/5256Y02A50/30
83
PatentIndex Score
5
Cited by
70
References
36
Claims

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.

Claims

exact text as granted — not AI-modified
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 the subject. 
     
     
       25. The method of  claim 24  wherein the subject is a human. 
     
     
       26. A method of inducing an immune response in a subject comprising administering an effective amount of the composition of  claim 18  to the subject. 
     
     
       27. The method of  claim 26  wherein the subject is a human. 
     
     
       28. A tetravalent vaccine comprising the composition of  claim 1 . 
     
     
       29. A tetravalent vaccine comprising the composition of  claim 17 . 
     
     
       30. A tetravalent vaccine comprising the composition of  claim 18 . 
     
     
       31. A method of preventing disease caused by dengue virus in a subject comprising administering an effective amount of the vaccine of  claim 28  to the subject. 
     
     
       32. The method of  claim 31  wherein the subject is a human. 
     
     
       33. A method of preventing disease caused by dengue virus in a subject comprising administering an effective amount of the vaccine of  claim 17  to the subject. 
     
     
       34. The method of  claim 33  wherein the subject is a human. 
     
     
       35. A method of preventing disease caused by dengue virus in a subject comprising administering an effective amount of the vaccine of  claim 18  to the subject. 
     
     
       36. The method of  claim 35  wherein the subject is a human.

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