Immunogenic HPV L2-containing VLPs and related compositions, constructs, and therapeutic methods
The invention provides immunotherapeutic and prophylactic bacteriophage viral-like particle (VLPs) which are useful in the treatment and prevention of human papillomavirus (HPV) infections and related disorders, including cervical cancer and persistent infections associated with HPV. Related compositions (e.g. vaccines), nucleic acid constructs, and therapeutic methods are also provided. VLPs and related compositions of the invention induce high titer antibody responses against HPV L2 and protect against HPV challenge in vivo. VLPs, VLP-containing compositions, and therapeutic methods of the invention induce an immunogenic response against HPV infection, confer immunity against HPV infection, protect against HPV infection, and reduce the likelihood of infection by HPV infection.
1. A PP7 RNA bacteriophage virus-like particle comprising a PP7 RNA bacteriophage single chain coat polypeptide dimer having an immunogenic papillomavirus (PV) L2 peptide insertion in the AB loop, the peptide insertion consisting essentially of the amino acid sequence corresponding to amino acids 17-31 of HPV16 L2 protein, which is displayed on the surface of the virus-like particle.
2. The RNA bacteriophage virus-like particle of claim 1 , wherein the L2 peptide insertion further comprises a second L2 peptide sequence from a second PV.
3. The RNA bacteriophage virus-like particle of claim 1 , further comprising a second RNA bacteriophage single chain coat polypeptide dimer having a second immunogenic papillomavirus (PV) L2 peptide insertion.
4. The RNA bacteriophage virus-like particle of claim 1 , wherein the second L2 peptide sequence corresponds to amino acids 17-31 of HPV16 is selected from HPV1, HPV5, HPV8, HPV35, HPV31, HPV33, HPV58, HPV52, HPV73, HPV6, HPV11, HPV18, HPV45, HPV39, HPV68, HPV59, HPV51, HPV56, HPV 66, HPV2, CPRV and BPV1.
5. An immunogenic composition comprising a bacteriophage virus-like particle of claim 1 .
6. A viral-like particle comprising a PP7 bacteriophage single chain coat polypeptide dimer having an HPV L2 peptide insertion consisting essentially of amino acids of SEQ ID NO:24, wherein the HPV L2 peptide is displayed on the virus-like particle.
7. A method for inducing an immune response to HPV in a subject comprising administering to the subject an RNA bacteriophage virus-like particle of claim 1 , wherein the composition induces a HPV-immunogenic response in the patient.
8. The RNA bacteriophage virus-like particle of claim 1 , wherein the immunogenic papillomavirus (PV) L2 peptide insertion has an amino acid sequence that is identical to amino acids 17-31 of HPV16 L2 protein.