US2014079704A1PendingUtilityA1

BI-Specific Diabodies For Masking And Targeting Vaccines

59
Assignee: TEXAS A & M UNIV SYSPriority: Sep 11, 2012Filed: Sep 11, 2013Published: Mar 20, 2014
Est. expirySep 11, 2032(~6.1 yrs left)· nominal 20-yr term from priority
Inventors:Waithaka MwangiSurya WaghelaLuc Berghman
C07K 16/116C07K 16/2851A61K 2039/55522C12N 2810/855C12N 2770/24334C07K 2317/76A61K 35/761C07K 2317/31C12N 2710/10343C07K 2317/626C07K 2317/622C07K 16/081A61K 39/42
59
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Claims

Abstract

The present invention describes compositions and methods for priming protective immunity in the presence of pre-existing maternal antibody. In some embodiments, the invention contemplates simultaneously masking vaccines to avoid antibody neutralization while targeting those vaccines to specific cell types in order to elicit an enhanced immune response. In other embodiments, vectors that recruit and activate specific antigen-presenting cells may further enhance the efficacy of those immune responses.

Claims

exact text as granted — not AI-modified
We claim: 
     
         1 . A bi-specific diabody comprising a viral antigen binding moiety fused in-frame with a cell surface antigen binding moiety. 
     
     
         2 . The diabody of  claim 1 , wherein said viral antigen binding moiety is a single chain antibody molecule that binds to bovine viral diarrhea virus. 
     
     
         3 . The diabody of  claim 2 , wherein said single chain antibody molecule binds to the bovine viral diarrhea virus protein E2. 
     
     
         4 . The diabody of  claim 1 , wherein said cell surface antigen binding moiety is a single chain antibody molecule that binds to dendritic cells. 
     
     
         5 . The diabody of  claim 4 , wherein said single chain antibody molecule binds to the bovine CD205 antigen receptor. 
     
     
         6 . A composition comprising a recombinant adenovirus that expresses Flt3L, GM-CSF and CD40L. 
     
     
         7 . A composition comprising a vaccine bound to the bi-specific diabody of  claim 1 . 
     
     
         8 . The composition of  claim 7 , wherein said vaccine is a bovine viral diarrhea virus 1 vaccine. 
     
     
         9 . The composition of  claim 7 , wherein said vaccine is a bovine viral diarrhea virus 2 vaccine. 
     
     
         10 . The composition of  claim 7 , wherein said vaccine is a mixture of bovine viral diarrhea virus 1 and bovine viral diarrhea virus 2 vaccines. 
     
     
         11 . The composition of  claim 7 , wherein said vaccine is a live vaccine. 
     
     
         12 . The composition of  claim 11 , wherein said live vaccine is a modified live vaccine. 
     
     
         13 . The composition of  claim 7 , wherein said vaccine is a live vectored vaccine. 
     
     
         14 . A composition comprising:
 a) a vaccine bound to the bi-specific diabody of  claim 1 , and   b) a recombinant adenovirus that expresses Flt3L, GM-CSF and CD40L.   
     
     
         15 . The composition of  claim 14 , wherein said vaccine is a bovine viral diarrhea virus 1 vaccine. 
     
     
         16 . The composition of  claim 14 , wherein said vaccine is a bovine viral diarrhea virus 2 vaccine. 
     
     
         17 . The composition of  claim 14 , wherein said vaccine is a mixture of bovine viral diarrhea virus 1 and bovine viral diarrhea virus 2 vaccines. 
     
     
         18 . The composition of  claim 14 , wherein said vaccine is a live vaccine. 
     
     
         19 . The composition of  claim 18 , wherein said live vaccine is a modified live vaccine. 
     
     
         20 . The composition of  claim 14 , wherein said vaccine is a live vectored vaccine. 
     
     
         21 . A method, comprising:
 a) providing:
 i) a subject at risk for infection by a virus, and 
 ii) a vaccine bound to the bi-specific diabody of  claim 1 ; and 
   administering said vaccine bound to said bi-specific diabody to said subject under conditions such that protective immunity is induced.   
     
     
         22 . The method of  claim 21 , wherein said subject is a bovine. 
     
     
         23 . The method of  claim 21 , wherein said subject is a neonatal calf. 
     
     
         24 . The method of  claim 21 , wherein said subject has neutralizing antibodies for said virus prior to administering said vaccine. 
     
     
         25 . The method of  claim 24 , wherein said neutralizing antibodies are maternal antibodies. 
     
     
         26 . The method of  claim 24 , wherein said neutralizing antibodies are bovine viral diarrhea virus 1-specific antibodies. 
     
     
         27 . The method of  claim 24 , wherein said neutralizing antibodies are bovine viral diarrhea virus 2-specific antibodies. 
     
     
         28 . The method of  claim 21 , wherein said vaccine is a bovine viral diarrhea virus 1 vaccine. 
     
     
         29 . The method of  claim 21 , wherein said vaccine is a bovine viral diarrhea virus 2 vaccine. 
     
     
         30 . The method of  claim 21 , wherein said vaccine is a mixture of bovine viral diarrhea virus 1 and bovine viral diarrhea virus 2 vaccines. 
     
     
         31 . The method of  claim 21 , wherein said vaccine is a live vaccine. 
     
     
         32 . The method of  claim 31 , wherein said live vaccine is a modified live vaccine. 
     
     
         33 . The method of  claim 21 , wherein said vaccine is a live vectored vaccine. 
     
     
         34 . A method, comprising:
 a) providing:
 i) a subject at risk for infection by a virus, 
 ii) a vaccine bound to the bi-specific diabody of  claim 1 , and 
 iii) a recombinant adenovirus that expresses Flt3L, GM-CSF and CD40L; and 
   b) administering said vaccine bound to said bi-specific diabody to said subject under conditions such that protective immunity is induced.   
     
     
         35 . The method of  claim 34 , wherein said subject is a bovine. 
     
     
         36 . The method of  claim 34 , wherein said subject is a neonatal calf. 
     
     
         37 . The method of  claim 34 , wherein said vaccine is a bovine viral diarrhea virus 1 vaccine. 
     
     
         38 . The method of  claim 34 , wherein said vaccine is a bovine viral diarrhea virus 2 vaccine. 
     
     
         39 . The method of  claim 34 , wherein said vaccine is a mixture of bovine viral diarrhea virus 1 and bovine viral diarrhea virus 2 vaccines. 
     
     
         40 . The method of  claim 34 , wherein said vaccine is a live vaccine. 
     
     
         41 . The method of  claim 40 , wherein said live vaccine is a modified live vaccine. 
     
     
         42 . The method of  claim 34 , wherein said vaccine is a live vectored vaccine. 
     
     
         43 . The method of  claim 34 , wherein said subject has neutralizing antibodies for said virus prior to administering said vaccine.

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