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. An MS2 RNA bacteriophage virus-like particle comprising a MS2 bacteriophage single chain coat polypeptide dimer having at least one human papillomavirus (HPV) L2 protein antigen corresponding to amino acids 17-31 of HPV type 16 L2 protein displayed on the N-terminus of the bacteriophage single chain coat polypeptide dimer.
2. The virus-like particle of claim 1 , wherein the HPV L2 protein antigen is a HPV type 16 L2 protein antigen.
3. The virus-like particle of claim 1 , wherein the HPV L2 protein antigen is an HPV type 1, 5, 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, or 59 L2 protein antigen.
4. The virus-like particle of claim 1 , wherein the RNA bacteriophage virus-like particle displays more than one HPV L2 protein antigen.
5. A composition comprising a population of virus-like particles of claim 1 .
6. A method for enhancing an immune response against an antigen in an animal comprising introducing the composition of claim 5 into said animal, wherein an enhanced immune response against said antigen is produced in said animal.
7. The method of claim 6 , wherein the composition is prophylactic for HPV-induced disorders.
8. The method of claim 6 , wherein said immune response is an enhanced B cell response and/or an enhanced T cell response.
9. The method of claim 6 , wherein said animal is a mammal.
10. The method of claim 6 , wherein said composition is introduced into said animal subcutaneously, intramuscularly, intravenously, intranasally, intravaginally or directly into the lymph node.
11. A vaccine comprising an immunologically effective amount of the composition of claim 5 together with a pharmaceutically acceptable diluent, carrier or excipient.
12. A method of immunizing or treating an animal comprising administering to said animal an immunologically effective amount of the vaccine of claim 11 .
13. The method of claim 12 , wherein said animal is a mammal.
14. The vaccine of claim 11 , wherein said vaccine further comprises an adjuvant.