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
1 European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
2 Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, USA
3 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany
4 Department of Molecular Immunology, Institutes of Molecular Medicine and Experimental Immunology (IMMEI), University of Bonn, Sigmund Freud Str. 25, D-53105 Bonn, Germany
5 Translational Immunology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany

© Juarez et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Translational Immunology, German Cancer Research Center DKFZ, Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany; Tel: +49 6221 567109; Fax: +49 6221 564773; E-mail:
# Present Address: AsteriaPharma, Mannheimer Str. 37, D-68723 Oftersheim, Germany


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.

Keywords: HPV, cervical cancer, HBsAg, synthetic genes, therapeutic vaccine, vaccine, VLP..