Recombinant vaccine viruses expressing il-15 and methods of using the same

Abstract

The invention is directed to compositions capable of augmenting the immunogenicity of a vaccine. The composition, or adjuvant, is administered to a mammal in need thereof in sequential or concurrent combination with a vaccine antigen. In one preferred aspect, the adjuvant is provided in the form of a recombinant poxvirus vector, such as a vaccinia virus vector, which comprises a nucleic acid sequence encoding IL-15.

What is claimed is: 
     
         1 - 38 . (canceled) 
     
     
         39 . A method for generating an immune response in an animal comprising administering an attenuated or nonvirulent vaccine virus vector comprising a nucleic acid sequence encoding mammalian IL-15 and an expression unit comprising a plurality of antigen encoding sequences operably linked to a first expression control sequence to an animal in an amount effective to stimulate the immune response. 
     
     
         40 . A method for generating an immune response in an animal comprising administering a vaccine composition comprising a nucleic acid sequence encoding mammalian IL-15 and an expression unit comprising a plurality of antigen encoding sequences operably linked to a first expression control sequence, to an animal in an amount effective to stimulate the immune response. 
     
     
         41 . The method of  claim 39  or  40 , wherein the immune response comprises one or more of: the production of memory CD8 +  T cells specific for the at least one antigen, the production of memory CD4 +  T cells specific for the at least one antigen, and the production of antibodies specific for the at least one antigen. 
     
     
         42 . The method of  claim 39  or  40 , wherein at least some of the antibodies are neutralizing antibodies. 
     
     
         43 .- 46 . (canceled) 
     
     
         47 . The method of  claim 39  or  40 , further comprising re-administering the nucleic acid encoding the antigen and nucleic acid encoding IL-15 after an interval of time, wherein the interval is at least about 6 months after the first administration. 
     
     
         48 . The method of  claim 39  or  40 , comprising re-administering the antigen after an interval of time, wherein the interval is at least about 8 months after the first administration. 
     
     
         49 . The method of  claim 39  or  40 , comprising re-administering the antigen after an interval of time, wherein the interval is at least about 10 months after the first administration. 
     
     
         50 . The method of  claim 39  or  40 , comprising re-administering the antigen after an interval of time, wherein the interval is at least about 12 months after the first administration. 
     
     
         51 . The method of  claim 39  or  40 , comprising re-administering the antigen after an interval of time, wherein the interval is at least about 14 months after the first administration. 
     
     
         52 . The method of  claim 39  or  40 , wherein the at least one antigen is a viral antigen. 
     
     
         53 . The method of  claim 52 , wherein the viral antigen is from an HIV virus. 
     
     
         54 . The method of  claim 39  or  40 , wherein the animal is at high risk of HIV infection. 
     
     
         55 . The method of  claim 39  or  40 , wherein the animal is not HIV positive at the time of first administration. 
     
     
         56 . The method of  claim 39  or  40 , wherein the animal is HIV positive at the time of first administration. 
     
     
         57 . The method of  claim 39  or  40 , wherein the expression unit comprises at least one CTL-recognized epitope, at least one T helper cell-recognized epitope, and at least one B cell-recognized epitope. 
     
     
         58 . The method of  claim 39  or  40 , wherein the vaccine virus is a poxvirus, wherein the expression control sequence comprises viral regulatory elements, wherein at least two antigens are from two different polypeptides, wherein the IL-15 encoding sequence is operably linked to a second expression control sequence, and wherein at least one antigen is an HIV, SIV, rabies, vaccinia, influenza, avian influenza, papillomavirus, cancer specific antigen, bacteria,  M. tuberculosis , anthrax, or malaria peptide or polypeptide. 
     
     
         59 . The method of  claim 39  or  40 , wherein at least one antigen is an HIV or SIV peptide or polypeptide. 
     
     
         60 . The method of  claim 39  or  40 , wherein at least one antigen is a rabies peptide or polypeptide. 
     
     
         61 . The method of  claim 39  or  40 , wherein at least one antigen is a vaccinia peptide or polypeptide and elicits a protective immune response against smallpox. 
     
     
         62 . The method of  claim 39  or  40 , wherein at least one antigen is a cancer specific antigen peptide or polypeptide. 
     
     
         63 . The method of  claim 62 , wherein the cancer specific antigen is from a Her-2/neu or prostate specific antigen polypeptide. 
     
     
         64 . The method of  claim 39  or  40 , wherein at least one antigen is a bacterial antigen. 
     
     
         65 . The method of  claim 39  or  40 , wherein at least two antigens are from two different clades of HIV. 
     
     
         66 . The method of  claim 57 , wherein the at least one antigen comprising a CTL-recognized epitope, the at least one antigen comprising a T helper cell-recognized epitope, and the at least one antigen comprising a B cell-recognized epitope are from the same HIV polypeptide. 
     
     
         67 . The method of  claim 39  or  40 , wherein the vaccine virus vector comprises one or more capsid polypeptides. 
     
     
         68 . The method of  claim 39  or  40 , wherein the antigen encoding sequence is expressed before the IL-15 encoding sequence. 
     
     
         69 . The method of  claim 39  or  40 , wherein the antigen encoding sequence is expressed after the IL-15 encoding sequence. 
     
     
         70 . The method of  claim 39  or  40 , wherein at least one antigen is selected from the group consisting of: an avian flu, human papillomavirus,  M. tuberculosis , anthrax or malaria. 
     
     
         71 . The method of  claim 39  or  40 , wherein the nucleic acid encoding at least one antigen is expressed by a second recombinant attenuated or nonvirulent vaccine virus vector.