Ii-key/antigenic epitope hybrid peptide vaccines
Disclosed is a nucleic acid molecule comprising a first expressible sequence encoding a protein of interest or polypeptide of interest which contains an MHC Class II-presented epitope, or said encoded protein or peptide. In addition, the nucleic acid molecule comprises a second expressible nucleic acid sequence encoding an antigen presentation enhancing hybrid polypeptide, or said encoded protein or peptide. The antigen presentation enhancing hybrid polypeptide includes the following elements: i) an N-terminal element consisting essentially of 4-16 residues of the mammalian Ii-Key peptide LRMKLPKPPKPVSKMR (SEQ ID NO: 1) and non-N-terminal deletion modifications thereof that retain antigen presentation enhancing activity; ii) a C-terminal element comprising an MHC Class II-presented epitope in the form of a polypeptide or peptidomimetic structure which binds to the antigenic peptide binding site of an MHC class II molecule, the MHC Class II-presented epitope being contained in the protein of interest of step a); and iii) an intervening peptidyl structure linking the N-terminal and C-terminal elements of the hybrid, the peptidyl structure having a length of about 20 amino acids or less.
1. A method for increasing the potency of a vaccine directed toward Influenza A strain H5N1 in a subject, the method comprising:
a) providing a vaccine, the vaccine comprising an epitope-containing protein or portion thereof which is encoded by the genome of the pathogen, or a DNA encoding the same;
b) providing an Ii-key hybrid construct comprising:
i. the LRMK residues of Ii-key protein; and
ii. an MHC class II epitope contained within the protein or portion thereof of step a), wherein said class II epitope is selected from a group consisting of the residues GLSLWMCSN [amino acid residues 8-16 of SEQ ID NO: 1167], residues FRNVIWLIK [amino acid residues 8-16 of SEQ ID NO: 1170] and the residues SGRMEFFWT [amino acid residues 8-16 of SEQ ID NO: 1159];
c) priming the immune system of the subject by administering the Ii-key construct of step b) under conditions appropriate for the stimulation of an immune response in the subject; and
d) administering the vaccine of step a) under conditions appropriate to boost the immune response of step c) thereby increasing the potency of the vaccine relative to a non-primed administration.
2. The method of claim 1 wherein the protein of step a) is produced by recombinant DNA technology.
3. The method of claim 1 wherein the subject is a mammal.
4. The method of claim 1 wherein the subject is a human.
5. The method of claim 1 wherein the MHC class II epitope consists of the residues GLSLWMCSN [amino acid residues 8-16 of SEQ ID NO: 1167].
6. The method of claim 1 wherein the MHC class II epitope consists of the residues FRNVIWLIK [amino acid residues 8-16 of SEQ ID NO: 1170].
7. The method of claim 1 wherein the MHC class II epitope consists of the residues SGRMEFFWT [amino acid residues 8-16 of SEQ ID NO: 1159].
8. The method of claim 1 , wherein both said vaccine and said Ii-key hybrid construct comprise peptides.