US2015265694A1PendingUtilityA1

Vaccines and methods for creating a vaccine for inducing immunity to all dengue virus serotypes

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Assignee: FLORIDA GULF COAST UNIVERSITY BOARD OF TRUSTEESPriority: Oct 25, 2011Filed: Oct 25, 2012Published: Sep 24, 2015
Est. expiryOct 25, 2031(~5.2 yrs left)· nominal 20-yr term from priority
Inventors:Sharon IsernScott F. Michael
A61K 39/12C07K 14/005C12N 2770/24134C07K 2319/00C12N 7/00A61K 2039/70C12N 2770/24151C07K 2319/40C12N 2770/24122A61P 31/14Y02A50/30
48
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Claims

Abstract

Described here is a method to produce a chimeric protein having portions of yellow fever virus and dengue virus. A small portion of the yellow fever virus 17D vaccine strain envelope protein (or other related flavivirus ) can be replaced by the corresponding portion from the dengue virus envelope protein. In some embodiments the chimeric protein may be used to create a treatment composition for DENV infection. In others, the chimeric protein may be used to create a vaccine that will induce broadly protective antibodies against dengue virus and reduce the induction of non-neutralizing antibodies that will cause enhancement.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of forming a chimeric protein, comprising the steps of:
 providing a yellow fever virus 17-D envelope protein having SEQ ID No. 1;   providing a dengue fever virus envelope protein selected from the group consisting of SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, or SEQ ID No. 5; and   substituting one or more of amino acids 1-11, 28-30, 32, 42, 44, 46, 70-81, 95-99, 110-115, 142-147, 149-157, 236-242, 304-324, 333, 335, 337, 350-352, 355, 356, 362-370, 377, 379, 386, 388-393 of SEQ ID No. 1 with the corresponding amino acid of the selected dengue fever virus envelope protein to create a chimeric envelope protein.   
     
     
         2 . The method of  claim 1 , wherein the substituted amino acids comprise the amino acids proximal to a Domain II fusion loop. 
     
     
         3 . The method of  claim 2 , wherein the substituted amino acids comprise the amino acids within 5 Å of the fusion loop. 
     
     
         4 . The method of  claim 2 , wherein the substituted amino acids comprise the amino acids within 14 Å of the fusion loop. 
     
     
         5 . A method of treating a dengue fever virus infection, the method comprising the step of administering the chimeric protein formed as in  claim 1 . 
     
     
         6 . A method of creating a treatment composition, comprising the steps of:
 providing a portion of an envelope protein from a  flavivirus;      providing a dengue fever virus envelope protein selecting from the group consisting of SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, or SEQ ID No. 5;   substituting a portion of the envelope protein amino acids of the  flavivirus  with a the corresponding envelope protein amino acids of the selected dengue fever virus to create a chimeric envelope protein;   providing a pharmaceutically acceptable excipient; and   mixing the chimeric envelope protein and the excipient.   
     
     
         7 . The method of  claim 6 , where the  flavivirus  is selected from the group consisting of West Nile Virus, St. Louis encephalitis, Dengue Fever virus, Japanese encephalitis, Yellow Fever virus, and Kunjin virus. 
     
     
         8 . The method of  claim 6 , wherein the substituted amino acids comprise the amino acids proximal to a fusion loop. 
     
     
         9 . The method of  claim 6 , wherein the substituted amino acids comprise the amino acids within 5 Å of the fusion loop. 
     
     
         10 . The method of  claim 6 , wherein the substituted amino acids comprise the amino acids within 14 Å of the fusion loop. 
     
     
         11 . A method of treating a dengue fever virus infection, the method comprising the step of administering the chimeric protein composition formed as in  claim 6 . 
     
     
         12 . A chimeric protein, comprising:
 an envelope protein comprised of yellow fever virus 17-D envelope protein having SEQ ID No. 1, wherein selected amino acids of the yellow fever virus 17-D envelope protein are substituted with corresponding amino acids of dengue fever virus envelope protein selected from the group consisting of SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, or SEQ ID No. 5.   
     
     
         13 . The chimeric protein of  claim 12 , wherein the substituted amino acids comprise the amino acids proximal to a Domain II fusion loop. 
     
     
         14 . The chimeric protein of  claim 12 , wherein the substituted amino acids comprise the amino acids within 5 Å of the fusion loop. 
     
     
         15 . The chimeric protein of  claim 12 , wherein the substituted amino acids comprise the amino acids within 14 Å of the fusion loop. 
     
     
         16 . The chimeric protein of  claim 12 , wherein one or more of amino acids 1-11, 28-30, 32, 42, 44, 46, 70-81, 95-99, 110-115, 142-147, 149-157, 236-242, 304-324, 333, 335, 337, 350-352, 355, 356, 362-370, 377, 379, 386, and 388-393 of SEQ ID No. 1 are substituted with the corresponding amino acids of the selected dengue fever virus envelope protein. 
     
     
         17 . A method of treating a dengue fever virus infection, the method comprising the step of administering the chimeric protein of  claim 12 . 
     
     
         18 . A composition for treatment of dengue fever virus, comprising:
 a chimeric envelope protein comprised of a  flavivirus  envelope protein, wherein selected amino acids of the  flavivirus  envelope protein are substituted with corresponding amino acids of dengue fever virus envelope protein selected from the group consisting of SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, or SEQ ID No. 5; and   a pharmaceutically acceptable excipient.   
     
     
         19 . The composition of  claim 18 , wherein the  flavivirus  is selected from the group consisting of West Nile Virus, St. Louis encephalitis, Dengue Fever virus, Japanese encephalitis, Yellow Fever virus, and Kunjin virus. 
     
     
         20 . The composition of  claim 18 , wherein the substituted amino acids comprise the amino acids proximal to a fusion loop. 
     
     
         21 . The composition of  claim 18 , wherein the substituted amino acids comprise the amino acids within 5 Å of the fusion loop. 
     
     
         22 . The composition of  claim 18 , wherein the substituted amino acids comprise the amino acids within 14 Å of the fusion loop. 
     
     
         23 . A method of treating a dengue fever virus infection, the method comprising the step of administering the chimeric protein of  claim 12 . 
     
     
         24 . A method of treating a dengue fever virus infection, the method comprising the step of administering the composition of  claim 18 .

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