Therapeutic and prophylactic vaccine for the treatment and prevention of papillomavirus infection

Abstract

Embodiments of the present invention provide compositions including a complexes of papillomavirus capsid polypeptide L2 and polypeptide including an immunotherapeutic epitope, and GST fusions thereof. Other embodiments also provide complexes comprising chimeras of papillomavirus L2 polypeptides non-covalently associated with papillomavirus L1 polypeptides, and GST fusions thereof. These compositions may be used to elicit immune responses in a patient to papillomavirus. Therapeutic and prophylactic vaccines for the prevention and treatment of viral infection, especially papillomavirus infection and cervical cancers and warts associated therewith, made from compositions of this invention, are also disclosed. Nucleic acids and expression vectors coding for compositions are also disclosed.

1 - 24 . (canceled) 
     
     
         25 . A method to elicit immune response against papillomavirus in a subject comprising, a) providing a polypeptide comprising one or more papillomavirus capsid L1 interaction sequence(s) comprising a first motif of Pro-Xaa (4)  to Xaa (10) -Pro followed by a second motif of Phe-Xaa-Leu-His-Pro or Tyr-Xaa-Leu-His-Pro; b) a particle having five papillomavirus capsid L1 polypeptides or truncated papillomavirus capsid L1 polypeptides, wherein the particle is assembled with the polypeptide during recombinant co-expression to form a non-covalently associated complex; c) administering the complex composition to the subject; wherein the administration is effective to induce an immune response against papillomavirus. 
     
     
         26 . The method in  claim 25 , wherein the truncated papillomavirus capsid L1 polypeptides comprise papillomavirus capsid L1 polypeptides having: a truncation up to 30 amino acids removed from a carboxy terminus, a truncation up to 9 amino acids removed from an amino terminus or point mutations at cysteines residues within the papillomavirus capsid L1 polypeptides. 
     
     
         27 . The method in  claim 25 , wherein papillomavirus capsid L1 polypeptides are selected from the group consisting of HPV6, HPV6a, HPV11, HPV16, HPV18, HPV30, HPV31, HPV33, HPV35, HPV39, HPV42, HPV43, HPV44, HPV45, HPV51, HPV52, HPV54, HPV55, HPV56, and HPV70 papillomavirus capsid L1 polypeptides. 
     
     
         28 . The method in  claim 25 , wherein papillomavirus capsid L1 polypeptides are selected from the group consisting of HPV6b, HPV11, HPV16, and HPV33 papillomavirus capsid L1 polypeptide. 
     
     
         29 . The method in  claim 25 , wherein the papillomavirus capsid L1 polypeptides are HPV11. 
     
     
         30 . The method of  claim 25 , wherein the one or more papillomavirus capsid L1 interaction sequence(s) comprises at least 90% identity corresponding to amino acid sequence beginning with amino acid 406 and ending with amino acid 439 of SEQ ID NO:1. 
     
     
         31 . The method of  claim 25 , wherein at least one of the one or more papillomavirus capsid L1 interaction sequence(s) corresponds to amino acid sequence beginning with amino acid 396 and ending with amino acid 439 of SEQ ID NO:1. 
     
     
         32 . The method of  claim 25 , wherein the one or more papillomavirus capsid L1 interaction sequence(s) further comprises a hydrophobic region. 
     
     
         33 . The method of  claim 25 , wherein the papillomavirus capsid L1 polypeptides comprise a point mutation corresponding to cysteine position 424 of SEQ ID NO:1. 
     
     
         34 . The method of  claim 25 , wherein there are 10 to 15 amino acids between the first motif and the second motif of the one or more papillomavirus capsid L1 interaction sequence(s). 
     
     
         35 . The method of  claim 25 , wherein the Xaa of the second motif is Tyr, Val, Thr or Glu. 
     
     
         36 . The method in  claim 25 , wherein the polypeptide further comprises at least one immunogenic epitope. 
     
     
         37 . A method to elicit immune response against a polypeptide in a subject comprising:
 a) providing a first polypeptide comprising one or more papillomavirus capsid L1 interaction sequence(s), the L1 interaction sequences comprise a first motif of Pro-Xaa (4)  to Xaa (10) -Pro followed by a second motif of Phe-Xaa-Leu-His-Pro or Tyr-Xaa-Leu-His-Pro;   b) a second polypeptide comprising at least one immunogenic epitope, wherein the first polypeptide is fused at its amino- or carboxy-terminus to the second polypeptide to form a chimeric protein;   c) a third polypeptide comprising five papillomavirus L1 capsid polypeptide or five truncated papillomavirus capsid L1 that form a capsomere non-covalently bound to the chimeric protein the chimeric protein and the third polypeptides form a complex; and   d) administering the complex composition to the subject; wherein the administration is effective to induce an immune response against the peptide.   
     
     
         38 . The method in  claim 37 , wherein the second polypeptide is selected from the group consisting of ras, EGFR, BRAC, Her2/neu, myc, abl, P1A, MAGE-1, MAGE-3, MAGE-6, BAGE, GAGE-1/2, GAGE-8, GAGE-6, RAGE-1, GnTV, mucin, connexin-37, ribosomal protein L9, gag IAP, gp70 env MuLV, p53, DEAD box helicase p68, c-akt, MUM-1, CDK4, beta-catenin, HLA-A2, bcr-abl, CASP-8 and KIAA0205 proteins. 
     
     
         39 . The method in  claim 37 , wherein the second polypeptide is selected from the group consisting of a mutant form of the ras, EGFR, BRAC, Her2/neu, myc, abl, P1A, MAGE-1, MAGE-3, MAGE-6, BAGE, GAGE-1/2, GAGE-8, GAGE-6, RAGE-1, GnTV, mucin, connexin-37, ribosomal protein L9, gag IAP, gp70 env MuLV, p53, DEAD box helicase p68, c-akt, MUM-1, CDK4, beta-catenin, HLA-A2, bcr-abl, CASP-8 or KIAA0205 proteins. 
     
     
         40 . The method of  claim 37 , wherein the second polypeptide is a viral oncogenic protein. 
     
     
         41 . The method of  claim 37 , wherein the second polypeptide is papillomavirus E7 protein. 
     
     
         42 . A nucleic acid sequence encoding a protein comprising:
 a) a first polypeptide comprising a papillomavirus capsid protein L1-interaction sequences(s) comprising a peptide having a first motif of Pro-Xaa (4)  to Xaa (10) -Pro followed by a second motif of Phe-Xaa-Leu-His-Pro or Tyr-Xaa-Leu-His-Pro; and   b) a second polypeptide comprising at least one immunogenic epitope, wherein the first polypeptide is fused at its amino- or carboxy-terminus to the second polypeptide to form a chimeric protein.   
     
     
         43 . The nucleic acid sequence of  claim 42 , wherein the second polypeptide is selected from the group consisting of ras, EGFR, BRAC, Her2/neu, myc, abl, P1A, MAGE-1, MAGE-3, MAGE-6, BAGE, GAGE-1/2, GAGE-8, GAGE-6, RAGE-1, GnTV, mucin, connexin-37, ribosomal protein L9, gag IAP, gp70 env MuLV, p53, DEAD box helicase p68, c-akt, MUM-1, CDK4, beta-catenin, HLA-A2, bcr-abl, CASP-8 and KIAA0205 proteins. 
     
     
         44 . The method in  claim 42 , wherein the second polypeptide is selected from the group consisting of a mutant form of the ras, EGFR, BRAC, Her2/neu, myc, abl, P1A, MAGE-1, MAGE-3, MAGE-6, BAGE, GAGE-1/2, GAGE-8, GAGE-6, RAGE-1, GnTV, mucin, connexin-37, ribosomal protein L9, gag IAP, gp70 env MuLV, p53, DEAD box helicase p68, c-akt, MUM-1, CDK4, beta-catenin, HLA-A2, bcr-abl, CASP-8 or KIAA0205 proteins.