Methods and reagents for vaccination which generate a CD8 T cell immune response

Abstract

New methods and reagents for vaccination are described which generate a CD8 T cell immune response against malarial and other antigens such as viral and tumour antigens. Novel vaccination regimes are described which employ a priming composition and a boosting composition, the boosting composition comprising a non-replicating or replication-impaired pox virus vector carrying at least one CD8 T cell epitope which is also present in the priming composition.

1 . A method for generating a CD8+ T cell immune response in a mammal against at least one target antigen, comprising administering to said mammal at least one dose of each of the following: 
 (i) a priming composition comprising a source of one or more CD8+ T cell epitopes of the target antigen; and    (ii) a boosting composition comprising a source of one or more CD8+ T cell epitopes of the target antigen, including at least one CD8+ T cell epitope which is the same as a CD8+ T cell epitope of the priming composition, wherein the source of CD8+T cell epitopes is a non-replicating or replication-impaired recombinant virus vector in the mammal;    with the proviso that if the source of epitopes in (i) is a viral vector, the viral vector in (ii) is derived from a different virus.    
     
     
         2 . The method according to  claim 1 , wherein the boosting composition of (ii) is delivered intravenously, intraepidermally or intradermally.  
     
     
         3 . The method of  claim 1  which further comprises administering an adjuvant.  
     
     
         4 . The method of  claim 3  wherein the adjuvant is SBAS2.  
     
     
         5 . The method of  claim 1  wherein the CD8+ T cell epitopes are one or more epitope strings comprising an amino acid sequence selected from the group consisting of: SEQ ID Nos: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42-64 or comprising an amino acid sequence encoded by a nucleotide sequence selected from the group consisting of: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.  
     
     
         6 . A method for generating a CD8+ T cell immune response in a mammal against at least one target antigen, comprising administering to said mammal at least one dose of each of the following: 
 (i) a priming composition comprising a source of one or more CD8+ T cell epitopes of the target antigen; and    (ii) a boosting composition comprising a source of one or more CD8+ T cell epitopes of the target antigen, including at least one CD8+ T cell epitope which is the same as a CD8+ T cell epitope of the priming composition, wherein the source of CD8+T cell epitopes is a recombinant avipox virus;    with the proviso that if the source of the epitopes in (i) is a viral vector, the viral vector in (ii) is derived from a different virus.    
     
     
         7 . The method of  claim 6  wherein the recombinant avipox virus is a recombinant fowlpox vector.  
     
     
         8 . The method of  claim 6  wherein the recombinant avipox virus is a recombinant canarypox vector.  
     
     
         9 . The method of  claim 8  wherein the recombinant canarypox vector is a recombinant ALVAC vector.  
     
     
         10 . The method of  claim 6  wherein the priming composition is a viral vector.  
     
     
         11 . The method of  claim 10  wherein the viral vector is a herpes viral vector.  
     
     
         12 . The method of  claim 10  wherein the viral vector is a replicating viral vector.  
     
     
         13 . The method of  claim 10  wherein the viral vector is a non-replicating viral vector.  
     
     
         14 . The method of  claim 6 , wherein the boosting composition is delivered intravenously, intraepidermally, intramuscularly, subcutaneously or intradermally.  
     
     
         15 . The method of  claim 6  which further comprises administering an adjuvant.  
     
     
         16 . The method of  claim 15  wherein the adjuvant is SBAS2.  
     
     
         17 . A method for generating a CD8+ T cell immune response in a mammal against at least one target antigen, comprising administering to said mammal at least one dose of each of the following: 
 (i) a priming composition comprising a source of one or more CD8+ T cell epitopes of the target antigen, wherein the priming composition is a DNA plasmid; and    (ii) a boosting composition comprising a source of one or more CD8+ T cell epitopes of the target antigen, including at least one CD8+ T cell epitope which is the same as a CD8+ T cell epitope of the priming composition, wherein the source of CD8+ T cell epitopes is a recombinant avipox virus.    
     
     
         18 . The method of  claim 17  wherein the recombinant avipox virus is a recombinant fowlpox vector.  
     
     
         19 . The method of  claim 17  wherein the recombinant avipox virus is a recombinant canarypox vector.  
     
     
         20 . The method of  claim 19  wherein the recombinant canarypox vector is a recombinant ALVAC vector.  
     
     
         21 . A method for generating a CD8+ T cell immune response in a mammal against a target antigen, comprising administering to said mammal at least one dose of a recombinant protein or particle comprising at least one naturally occurring epitope or antigen of the target antigen, followed by at least one dose of a recombinant avipox virus encoding the same epitope or antigen.  
     
     
         22 . The method of  claim 21  wherein the recombinant avipox virus is a recombinant fowlpox vector.  
     
     
         23 . The method of  claim 21  wherein the recombinant avipox virus is a recombinant canarypox vector.  
     
     
         24 . The method of  claim 23  wherein the recombinant canarypox vector is a recombinant ALVAC vector.  
     
     
         25 . The method of  claim 21  wherein the recombinant protein or particle is a virus-like particle (VLP).  
     
     
         26 . The method of  claim 25  wherein the VLP is Ty VLP.  
     
     
         27 . A method for generating a CD8+ T cell immune response against malaria in a mammal, comprising administering to said mammal at least one dose of each of the following: 
 a) a priming composition comprising a source of one or more CD8+ T cell epitopes of malaria; and    b) a boosting composition comprising a source of one or more CD8+ T cell epitopes of malaria, including at least one CD8+ T cell epitope which is the same as a CD8+ T cell epitope of the priming composition, wherein the source of CD8+ T cell epitopes is a recombinant avipox vector in the mammal;    with the proviso that if the source of epitopes in (i) is a viral vector, the viral vector in (ii) is derived from a different virus.    
     
     
         28 . The method of  claim 27  wherein the recombinant avipox virus is a recombinant fowlpox vector.  
     
     
         29 . The method of  claim 27  wherein the recombinant avipox virus is a recombinant canarypox vector.  
     
     
         30 . The method of  claim 29  wherein the recombinant canarypox vector is a recombinant ALVAC vector.  
     
     
         31 . The method of  claim 27  wherein the CD8+ T cell epitopes are one or more epitope strings comprising an amino acid sequence selected from the group consisting of: 
 SEQ ID Nos: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40 and 42-64 or comprising an amino acid sequence encoded by a nucleotide sequence selected from the group consisting of: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39.  
 
     
     
         32 . The method of  claim 27  which further comprises administering an adjuvant.  
     
     
         33 . The method of  claim 32  wherein the adjuvant is SBAS2.  
     
     
         34 . The method of  claim 27  wherein the priming composition is a DNA plasmid.  
     
     
         35 . The method of  claim 27  wherein the priming composition is a recombinant protein or particle.