Virus-Like Particles Harboring CCL19, IL-2 and HPV16 E7 Elicit Protective T Cell Responses in HLA-A2 Transgenic Mice
Victoria Juarez 1, #, H Amalia Pasolli2, Andrea Hellwig 3, Natalio Garbi 4, Angel Cid Arregui*, 5
Identifiers and Pagination:Year: 2012
Issue: Suppl 2
First Page: 270
Last Page: 276
Publisher Id: TOVJ-6-270
Article History:Received Date: 15/9/2012
Revision Received Date: 12/11/2012
Acceptance Date: 15/11/2012
Electronic publication date: 28/12/2012
Collection year: 2012
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Infection by high-risk genotypes of human papillomaviruses (HR-HPVs) is the cause of cancer of the uterine cervix. Although prophylactic vaccines directed against the two most prevalent HR-HPV types (HPV16 and 18) have been commercialized recently, there is a need for effective therapeutic vaccines against HR-HPVs. We have tested in mice a chimeric protein composed of the hepatitis B small surface antigen (HBsAg(S)) flanked at its N-terminus by chemokine CC ligand 19/macrophage inflammatory protein-3β (CCL19/MIP-3β), and at the C-terminus by interleukin 2 (IL-2) and an artificial HPV16 E7 polytope. This protein is assembled into nanoparticles and both CCL19 and IL-2 conserve their functionality. HLA-A2 (AAD) transgenic mice immunized with a plasmid encoding this protein mounted specific T cell responses against E7 without the need of an adjuvant. Furthermore, vaccination prevented the development of tumors after implantation of the E6/E7-expressing TC-1/A2 tumor cell line. Our results suggest that vaccines based on HBsAg(S) nanoparticles carrying short E7 epitopes and immune-stimulatory domains might be of therapeutic value in the treatment of patients suffering from cervical pre-cancer or cancer lesions caused by HR-HPVs.