Settings for recombinant adenoviral-based vaccines

Abstract

The present invention provides new uses of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, the invention provides new assays to determine the best regimen for applying the most suitable recombinant viral vector in a vaccination or gene therapy setting.

1 .- 38 . (canceled) 
     
     
         39 . A method for determining a titer of neutralizing antibodies in a human- or animal-derived blood sample, the method comprising:
 obtaining a blood sample of the human or animal;   culturing host cells;   adding the blood sample to the host cell culture;   introducing recombinant viruses to the host cell culture, wherein the recombinant viruses comprise a transgene encoding a protein, and wherein the recombinant viruses are able to infect the host cells in the absence of neutralizing antibodies;   determining the abundance or activity of the protein; and   comparing the abundance or activity of the protein to a control, thereby determining the titer of neutralizing antibodies in the blood sample.   
     
     
         40 . The method according to  claim 39 , wherein the recombinant viruses are adenoviruses, and wherein the neutralizing antibodies are directed against adenoviruses. 
     
     
         41 . The method according to  claim 39 , wherein the determined abundance or activity of the protein is compared to a standard value. 
     
     
         42 . The method according to  claim 39 , wherein the protein is selected from the group consisting of luciferase, Green Fluorescent Protein, and LacZ. 
     
     
         43 . The method according to  claim 39 , wherein the host cells comprise A549 cells. 
     
     
         44 . The method according to  claim 39 , wherein the sample added to the host cells is a diluted sample. 
     
     
         45 . A method for determining a titer of neutralizing antibodies in a human- or animal-derived blood sample, the method comprising:
 obtaining a blood sample of the human or animal;   culturing host cells;   adding the blood sample to the host cells;   introducing viruses comprising a viral genome into the host cell culture, wherein the viruses are able to infect the host cells in the absence of neutralizing antibodies;   determining the number of viral genomes per cell; and   comparing the number of viral genomes per cell to a control, thereby determining the titer of neutralizing antibodies in the blood sample.   
     
     
         46 . The method according to  claim 45 , wherein the viruses are able to replicate in the host cells in the absence of neutralizing antibodies. 
     
     
         47 . The method according to  claim 45 , wherein the viruses are adenoviruses, and wherein the neutralizing antibodies are directed against adenoviruses. 
     
     
         48 . The method according to  claim 47 , wherein the adenoviruses are recombinant adenoviruses. 
     
     
         49 . The method according to  claim 48 , wherein the recombinant adenoviruses are replication-defective. 
     
     
         50 . The method according to  claim 45 , wherein the number of viral genomes is compared to a standard value. 
     
     
         51 . The method according to  claim 45 , wherein the host cells comprise A549 cells. 
     
     
         52 . The method according to  claim 45 , wherein the sample added to the host cells is a diluted sample. 
     
     
         53 . The method according to  claim 45 , wherein the number of viral genomes per cell is determined by a quantitative polymerase chain reaction.