Expression vectors for stimulating an immune response and methods of using the same

Abstract

The present invention relates to nucleic acid vaccines encoding multiple CTL and HTL epitopes and MHC targeting sequences.

1 . An expression system which comprises a promoter operably linked to a nucleotide sequence which encodes a peptide comprising a first amino acid sequence which is a major histocompatibility (MHC) targeting sequence fused to a second amino acid sequence encoding a Class I MHC restricted CTL peptide epitope and an HTL peptide epitope, wherein the CTL peptide epitope is selected from the group consisting of  P. falciparum  CTL peptide epitopes set forth as SEQ ID NOs: 429-443, 445-448, and 450-461, and an analog of each of the foregoing CTL peptide epitopes.  
     
     
         2 . The expression system of  claim 1 , wherein the HTL peptide epitope is a universal HTL peptide epitope.  
     
     
         3 . The method expression system of  claim 2 , wherein the universal HTL peptide epitope is a panDR epitope.  
     
     
         4 . The method expression system of  claim 3 , wherein the panDR epitope comprises the sequence Ala Lys Phe Val Ala Ala Trp Thr Leu Lys Ala Ala Ala (SEQ ID NO: 52).  
     
     
         5 . The method expression system of  claim 1 , wherein the HTL peptide epitope is a  P. falciparum  HTL peptide epitope.  
     
     
         6 . The method expression system of  claim 5 , wherein the  P. falciparum  HTL peptide epitope is selected from the group consisting of HTL peptide epitopes set forth as SEQ ID NOs: 413-428, and an analog of each of the foregoing HTL peptide epitopes.  
     
     
         7 . The method expression system of  claim 1 , wherein the MHC targeting sequence is the signal sequence from Ig kappa.  
     
     
         8 . The method expression system of  claim 1 , wherein the MHC targeting sequence is the signal sequence from insulin.  
     
     
         9 . The method expression system of  claim 1 , wherein the MHC targeting sequence is the signal sequence from tissue plasminogen.  
     
     
         10 . The method expression system of  claim 1 , wherein the MHC targeting sequence is the signal sequence from LAMP-1.  
     
     
         11 . A method to induce an immune response in a subject which comprises administering to a mammalian subject the expression system of  claim 1 .  
     
     
         12 . An expression system which comprises a promoter operably linked to a nucleotide sequence which encodes a peptide comprising a first amino acid sequence which is a MHC targeting sequence fused to a second amino acid sequence encoding a class 1 MHC restricted CTL peptide epitope and  P. falciparum  HTL peptide epitope, wherein the  P. falciparum  HTL peptide epitope is selected from the group consisting of  P. falciparum  HTL peptide epitopes set forth as SEQ ID NOs: 413-428, and an analog of each of the foregoing HTL peptide epitopes.  
     
     
         13 . The expression system of  claim 12 , wherein the CTL peptide epitope is an  P. falciparum  CTL peptide epitope.  
     
     
         14 . The expression system of  claim 13 , wherein the CTL peptide epitope is an A2 peptide epitope.  
     
     
         15 . The expression system of  claim 13 , wherein the CTL peptide epitope is an A3 peptide epitope.  
     
     
         16 . The expression system of  claim 13 , wherein the CTL peptide epitope is a B7 peptide epitope.  
     
     
         17 . The expression system of  claim 13 , wherein the CTL peptide epitope is selected from the group consisting of CTL peptide epitopes set forth as SEQ ID Nos: 429-443, 445-448, and 450-461, and an analog of each of the foregoing CTL peptide epitopes.  
     
     
         18 . The method expression system of  claim 12 , wherein the MHC targeting sequence is the signal sequence from Ig kappa.  
     
     
         19 . The method expression system of  claim 12 , wherein the MHC targeting sequence is the signal sequence from insulin.  
     
     
         20 . The method expression system of  claim 12 , wherein the MHC targeting sequence is the signal sequence from tissue plasminogen.  
     
     
         21 . The method expression system of  claim 12 , wherein the MHC targeting sequence is the signal sequence from LAMP-1.  
     
     
         22 . A method to induce an immune response in a subject which comprises administering to a mammalian subject the expression system of  claim 12.