Cd40 ligand fusion protein vaccine

Abstract

Provided are methods of generating an immune response to any of various antigens including foreign antigens such as infectious agent antigens. In general, the method comprises administering an expression vector encoding a transcription unit encoding a secretable fusion protein, the fusion protein containing the foreign antigen and CD40 ligand and also administering the encoded fusion protein. In another approach, an immune response to the foreign antigen is elicited using the encoded fusion protein without administering the vector. The invention methods may be used to immunize an individual against an infectious agent such as influenza virus. Methods of obtaining an immune response in older individuals also is described.

What is claimed is: 
     
         1 . A vaccine composition for generating an immune response in an individual against one or more foreign antigens on an infectious agent, comprising:
 a secretable fusion protein comprising a first of two or more foreign antigen fragments from the extracellular domain of said one or more foreign antigens, each of said foreign antigen fragments comprising at least two epitopes, said foreign antigen fragments to be linked to the amino terminus of an extracellular domain of a CD40 ligand, for generating both a cellular and antibody immune response, wherein   the first one of said foreign antigen fragments contains a first epitope that includes an antigenic determinant binding site that is recognized and bound by Class II MHC, and   the first one of said foreign antigen fragments further contains a second epitope that includes an antigenic determinant binding site that is recognized and bound by Class I MHC,   said fusion protein further comprising a second one of said foreign antigen fragments that contains a third epitope and a fourth epitope, each epitope respectively includes a binding site that is respectively recognized and bound by Class I MHC and Class II MHC, wherein   said epitopes in the second foreign antigen fragment having a distinct amino acid sequence from the amino acid sequence in the first foreign antigen fragment.   
     
     
         2 . The vaccine composition of  claim 1  wherein said one or more foreign antigens on an infectious agent comprise at least one or more proteins of the same strain or different strains. 
     
     
         3 . The vaccine composition of  claim 1 , wherein the first and second foreign antigen fragments are each from a different protein of the infectious agent. 
     
     
         4 . The vaccine composition of  claim 1  including wherein each of said amino acid foreign antigen fragments has a size such that the stability of a trimeric CD40 ligand, to which the foreign antigen fragments are attached, will not be disrupted. 
     
     
         5 . The vaccine composition of  claim 1  wherein fusion protein is a non-viral plasmid DNA. 
     
     
         6 . The vaccine composition of  claim 1  wherein said foreign antigen fragments are one of bacterial, fungal, viral or protozoan. 
     
     
         7 . A vaccine composition for generating an immune response in an individual against one or more foreign antigens on an infectious agent, comprising:
 a first secretable fusion protein comprising two or more first epitopes from the extracellular domain of a first one of two or more foreign antigens linked to the amino terminus of an extracellular domain of a CD40 ligand, for generating both a cellular and humoral immune response, wherein one of said first epitopes includes an antigenic determinant binding site that is recognized and bound by Class I MHC and the other of said first epitopes includes an antigenic determinant binding site that is recognized and bound by Class II MHC,   a second secretable fusion protein comprising two or more second epitopes from the extracellular domain of a second one of said two or more foreign antigens linked to the amino terminus of an extracellular domain of a CD40 ligand, for generating both a cellular and humoral immune response, wherein one of said second epitopes includes an antigenic determinant binding site that is recognized and bound by Class I MHC and the other of said second epitopes includes an antigenic determinant binding site that is recognized and bound by Class II MHC, and   wherein each of said first and second epitopes are from a different protein of the infectious agent and are distinct one from the other and said first secretable fusion protein and second secretable fusion protein, collectively define said vaccine composition.   
     
     
         8 . A pharmaceutical vaccine mixture of two or more expression vectors comprising:
 a first expression vector containing one or more fragments of a first protein fused to an extracellular domain of a CD40 ligand defining a first fusion protein of an infectious agent and where the one or more fragments contain at least two binding sites where one site binds to class I MHC and the other site binds to class II MHC, for respectively generating a cellular and humoral immune response, and   a second expression vector containing one or more fragments of a second protein of the infectious agent different from said first protein, where the one or more fragments contain at least two binding sites that bind to class I MHC and class II MHC, for respectively generating a cellular and humoral immune response